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Previously a page with references to studies on the Etiology, Incidence and Prevention of Asherman's syndrome was added. Click here or on the relevant tab in the menu above for more.
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Showing posts with label IUA. Show all posts
Showing posts with label IUA. Show all posts
Tuesday, January 25, 2011
Wednesday, September 29, 2010
Effect of Asherman’s syndrome on infant health
Over a century after the condition was first reported, there are as of yet no analytical studies on the health of children born to women with a history of AS or even on pregnancies conceived with adhesions present. The only data available in the literature are from isolated case reports.
As mentioned elsewhere, the proportion of births after Asherman’s syndrome treatment (ie. births / total number of women treated) are around 40% across all classifications. Reproductive outcome is correlated with severity at diagnosis, with mild cases having a highest live birth ‘rates’ (‘proportion’ is actually the correct terminology) and severe cases having the lowest live birth proportion.
The risks associated with abnormally invasive placenta (accreta, percreta, increta) and low lying placenta (previa) mainly affect the mother at delivery. These can lead to significant blood loss and emergency hysterectomy. Massive hemorrhaging is a life threatening situation for the mother and requires blood transfusions. Conversely, IUGR, preterm birth and IC present a risk for the fetus.
The majority of gestations following the surgical correction of adhesions are uncomplicated and presumably healthy babies are delivered. This is partly because most women who are able to carry pregnancies have an adhesion free uterus with relatively healthy endometrium while in those with severe endometrial injury (resulting in IUA with or without fibrosis) pregnancy is less likely even after surgery, and any pregnancy achieved would generally miscarry early on.
A retrospective case control study found no difference in pregnancy outcome aside from birthweight in pregnancies with and without IUA (1). It should be noted that case-control studies and in general, retrospective studies are not the most rigorous in terms of evidence. Presumably, the extent, severity and location of uterine adhesions affect the course and outcome of the pregnancy. However, if adhesions are only mild and filmy they can stretch or even divide as the uterus grows with the pregnancy. The latter was described in a case report by Klatsky et al (2) (see cases below). As no two cases of AS are identical, it is difficult to predict the outcome and therefore close monitoring of the pregnancy by a high risk obstetrician is advised for regular screening for potential complications such as cervical incompetence, IUGR, premature labour, invasive placenta, and pre eclampsia. Regular screening will also assist in the detection of fetal abnormalities and potentially improve their management. Home births are not advisable in women with past AS even if the pregnancy appears to be progressing without problems, as invasive placenta may not be detected until the time of delivery and this could lead to serious life threatening situations.
Prematurity and neonatal complications
Most health complications in newborns delivered to women with past (or current) AS would probably be related to prematurity, as women with AS (past or current) are more likely to deliver preterm. Prematurity may be caused by other known complications associated with AS such as IUGR. Depending on the extent of prematurity, such birth defects could include neurological problems (eg. cerebral palsy, apnea of prematurity, retinopathy of prematurity), respiratory problems (eg. respiratory distress syndrome), cardiovascular problems (eg. patent ductus arteriosus), gastrointestinal/metabolic disorders (eg. rickets, inguinal hernia), hematological conditions (eg. jaundice, anemia) and infections (eg. sepsis, UTI). Obviously neonatal mortality is another possible complication of premature birth and generally, the earlier the birth, the more severe the complications. Babies born during the second trimester due to cervical incompetence (as a result of previous cervical dilations associated with the index injury leading to AS and/or surgical correction of AS) are often too young to survive outside the body, and even if they do they will have severe and life long complications.
Effect of IUA during pregnancy: four case reports with different outcomes
It is very important that the uterus is assessed for adhesions after treatment of Asherman’s syndrome before conception is attempted/advised. Adhesions are known to recur in moderate and severe cases, and further surgery may be required. Complications will be increased if pregnancy occurs in the presence of thick adhesions. This is highlighted in the examples from case reports below. Note that the first example is one where the patient underwent endometrial ablation (EA) which is a procedure that mimics very severe AS. It is unclear whether the patient was counseled for the risks of a future pregnancy. Usually both IUA and extensive fibrosis are present. In fibrosis the endometrium is replaced with scar tissue to varying extents (hence it is also known as sclerotic endometrium or ‘unstuck’ Asherman’s syndrome due to the absence of adhesions). This is the most severe form of AS. Fibrosis occurs mainly as a result of thermal energy use in the uterus. Electrosurgery (e.g. resectoscope, laser etc.) also leads to IUA because of damage to the basal endometrium. EA is procedure used to treat abnormally heavy bleeding in which the endometrium is intentionally and irreversibly destroyed using thermal ablation. First reported in 1981, EA has been gaining popularity as a less invasive alternative to hysterectomy. Unfortunately damage may also occur unintentionally when these same instruments are used for other purposes such as the resectioning of uterine fibroids or polyps or the dissection of adhesions during the treatment of Asherman’s syndrome. Instead of having their fertility restored, the patient may end up with more severe adhesions and fibrosis than originally. Therefore mechanical dissection of adhesions may have better outcomes. EA should not be undertaken in women who desire future fertility and they should be informed about potential dangers of pregnancies if they fall pregnant. I have seen doctors on the internet advertizing endometrial ablation reversal in women who wish to conceive after having had the procedure. This practice is highly questionable given the high risk of severe pregnancy complications and the low chance of a live birth after EA. Pregnancy rates following EA are in the vicinity of 0.2-0.7% (3,4) with perinatal mortality reported to be 11.8% (4)
Severe AS from EA and birth defects
1. Mukul and Linn (5) reported amniotic band syndrome (ABS) in a pregnancy following endometrial ablation. The patient had three prior pregnancies and one birth. ABS , also called Amniotic Constriction Band Syndrome, is a set of congenital birth defects believed to be caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero. The patient had undergone rollerball EA 7 years earlier without complications. Ultrasonography at 7 weeks revealed evidence of amniotic band syndrome: synechiae (i.e. IUA) were seen in the midquadrant of the uterus, creating amniotic sheets and bands with small compartments. The entire lower uterine segment was empty except for the right leg and a loop of umbilical cord poking through the lower uterine synechia. The fetus was of normal size but with clubbed feet, a distorted spine, and ventriculomegaly.
The patient underwent preterm labour and membranes ruptured at 26 weeks. A male infant was delivered via emergency C-section. An emergency hysterectomy was performed. The infant’s birth defects were described as follows:
“There were positional deformities in the neck, an asymmetric chest, severe scoliosis confirmed by X-ray, bilateral clubbed feet, and very limited movement of all long extremities consistent with arthrogryposis. The right lower extremity was swollen, cyanotic, denuded of skin, and without perfusion or pulses. Areas of significant necrosis on the posterior thigh of the right lower extremity were noted.”
Prognosis was poor and the parents decided to withdraw ventilation support. The infant died 6 hours after delivery.
One theory on the cause of ABS is that it occurs when the inner membrane (amnion) ruptures without injury to the outer membrane (chorion), exposing the fetus to fibrous tissue (bands) from the ruptured amnion which can entangle body parts, leading to congenital abnormalities. Another theory is that vascular disruption occurs. The latter would explain the presence of cleft lip in ABS cases. Either theory could account for its description in women with severe injury to the endometrium. Both IUA and fibrosis resulting from EA would lead to vascular disruption.
Mild to moderate IUA during pregnancy
In the three examples below, patients developed IUA from uterine curettage (i.e. D&C). One case ended in the term birth of a healthy baby while the other two resulted in congenital abnormalities. It appears that the severity of the adhesions affects outcome.
2. Klatsky et al (3) report of a pregnancy complicated by endometrial scarring which ended in a term birth of a healthy infant. The patient, a 39 year old woman, had a history of D&C for therapeutic abortion followed by three miscarriages, the last of which was completed by D&C. An ultrasound at 19 weeks identified a thick band crossing the lower uterine segment with the placenta inserting alongside it. Mullerian fusion anomalies were ruled out. Doppler flow imaging demonstrated flow along the synechia to the overlying placenta. At 25 weeks the patient passed half a cup of bright red blood. An ultrasound revealed a thinning scar with placenta still implanted on both sides and a small subchorionic hematoma. At 31 weeks ultrasound demonstrated a reduced scar with placenta visible on only one side. The patient presented at term with premature rupture of the membranes and a fetus in breech presentation. She underwent cesarean delivery. No uterine anomalies or adhesions were found, presumabley the thin uterine adhesion was evacuated with the placenta. The infant had no morphological abnormalities.
3. Deering et al (6) report a case of head entrapment of a second twin by intrauterine synechiae leading to long term health complications. The 40 year old patient had a history of two uterine curettages (ie. D&C) , one for first trimester miscarriage and a second for menorrhagia. CVS was undertaken during first trimester revealing normal male karyotypes. Diagnostic hysteroscopy and lysis of adhesions was not performed prior to IVF resulting in a twin pregnancy. She presented at 19 weeks for evaluation due to a shortened cervix and pronounced funneling (symptoms of cervical insufficiency). A McDonald cerclage was placed. Ultrasound examination also revealed a moderate sized uterine synechiae wrapped around the neck and placenta of twin B. Twin B was affected by IUGR, weighing less than the third percentile for gestational age. The development of growth restriction and discordance in twin B is thought to result from the combination of the contracted space available for twin B’s head to grow, the compression of the umbilical cord against the fetal neck by the uterine band, and the implantation of the placenta in an abnormal portion of the uterus with a potentially inadequate blood supply.
Cesarean delivery was undertaken at 26 weeks due to fetal distress of twin B and head entrapment. As seen on ultrasonography a thick uterine band was tightly constricting the neck of twin B. The location of the tissue was consistent with the uterine synechia observed on hysterosalpingogram before IVF. Twin A did well and was discharged from the NICU at 3 months. Twin B remained in the NICU until 5 months of age, at which time he was discharged to a longer-term pediatric care facility for continued care. This case demonstrates that significant uterine synechia might result in intrauterine head entrapment, as well as IUGR.
4. Baumler et al (7) report a case of premature birth of an infant with prolonged pulmonary distress syndrome and severe kyphoscoliosis (90 degrees) in a patient with IUA. The patient was 37 years of age with a history of two first trimester miscarriages and evacuation of retained products of conception (ERPC or D&C). Preterm labor occurred at 28 weeks. Midtrimester 2D, 3D and real-time 4D ultrasound revealed a horizontal miduterine separation in the form of an ‘egg-timer’. The uterine cavity was separated in two superimposed cavities. The fetus and the placenta were located in the upper part of the uterus, and the right arm of the fetus and part of the umbilical cord extended in the lower part of the uterus, through an opening in the separating horizontal membrane. The kyphoscoliosis, thought to be due to severe oligoamnios was managed conservatively.
The mother’s operative hysteroscopy carried out 6 months later confirmed both clinically and histologically the presence of a transversal muscular synechia.
The examples above illustrate the importance of diagnosing and removing IUA prior to IVF or conception. Furthermore, thick adhesions restrict the growth of the uterus, possibly increasing pressure on the cervix and leading to CI or preterm labor. The patient in the example above (6) may not even have needed IVF as her fertility problems may have been due to Asherman’s syndrome which could have been surgically corrected and allowed a better pregnancy outcome. Not only are the chances of pregnancy reduced, the health of the mother and infant are compromised as well with the presence of IUA. It is particularly irresponsible to perform IVF in patients without confirming an architecturally normal uterus. There is unfortunately a tendency for some clinicians to believe that IUA are harmless and asymptomatic (3) but this case shows that even a single thick band can have significant repercussions during pregnancy. As all cases are not treatable, in particular more severe ones where there is a tendency for scars to reform and irreversible fibrosis to occur, prevention of AS wherever possible is the best and easiest strategy available.
REFERENCES
1. Ball RH, Buchmeier SE, Longnecker M. Clinical significance of sonographically detected uterine synechiae in pregnant patients. J Ultrasound Med. 1997 Jul;16(7):465-9. Abstract
2. Klatsky PC, Tran ND, Strachowski L. A pregnancy complicated by endometrial scarring. Fertil Steril. 2009 Jun;91(6):2707-8. Epub 2008 Nov 20 Abstract
3. Cook JR, Seman E. Pregnancy following endometrial ablation: case history and literature review. Obstet Gynecol Surv 2003;58:551– 6. Abstract
4. Pugh CP, Crane JM, Hogan TG. Successful intrauterine pregnancy after endometrial ablation. J Am Assoc Gynecol Laparosc 2000;7:391– 4. Abstract
5 Mukul LV, Linn JG. Pregnancy complicated by uterine synechiae after endometrial ablation. Obstet Gynecol. 2005 May;105(5 Pt 2):1179-82. Abstract
6 Deering SH, Heller J, Winkel C, Landy HJ. Intrauterine head entrapment of a second twin by a uterine synechia. Obstet Gynecol. 2003 Oct;102(4):693-5. Abstract
7 Bäumler M, Faure JM, Couture A, Flunker S, Boulot P. Prenatal 3D ultrasound and MRI assessment of horizontal uterine synechia. Prenat Diagn. 2008 Sep;28(9):874-5.
As mentioned elsewhere, the proportion of births after Asherman’s syndrome treatment (ie. births / total number of women treated) are around 40% across all classifications. Reproductive outcome is correlated with severity at diagnosis, with mild cases having a highest live birth ‘rates’ (‘proportion’ is actually the correct terminology) and severe cases having the lowest live birth proportion.
The risks associated with abnormally invasive placenta (accreta, percreta, increta) and low lying placenta (previa) mainly affect the mother at delivery. These can lead to significant blood loss and emergency hysterectomy. Massive hemorrhaging is a life threatening situation for the mother and requires blood transfusions. Conversely, IUGR, preterm birth and IC present a risk for the fetus.
The majority of gestations following the surgical correction of adhesions are uncomplicated and presumably healthy babies are delivered. This is partly because most women who are able to carry pregnancies have an adhesion free uterus with relatively healthy endometrium while in those with severe endometrial injury (resulting in IUA with or without fibrosis) pregnancy is less likely even after surgery, and any pregnancy achieved would generally miscarry early on.
A retrospective case control study found no difference in pregnancy outcome aside from birthweight in pregnancies with and without IUA (1). It should be noted that case-control studies and in general, retrospective studies are not the most rigorous in terms of evidence. Presumably, the extent, severity and location of uterine adhesions affect the course and outcome of the pregnancy. However, if adhesions are only mild and filmy they can stretch or even divide as the uterus grows with the pregnancy. The latter was described in a case report by Klatsky et al (2) (see cases below). As no two cases of AS are identical, it is difficult to predict the outcome and therefore close monitoring of the pregnancy by a high risk obstetrician is advised for regular screening for potential complications such as cervical incompetence, IUGR, premature labour, invasive placenta, and pre eclampsia. Regular screening will also assist in the detection of fetal abnormalities and potentially improve their management. Home births are not advisable in women with past AS even if the pregnancy appears to be progressing without problems, as invasive placenta may not be detected until the time of delivery and this could lead to serious life threatening situations.
Prematurity and neonatal complications
Most health complications in newborns delivered to women with past (or current) AS would probably be related to prematurity, as women with AS (past or current) are more likely to deliver preterm. Prematurity may be caused by other known complications associated with AS such as IUGR. Depending on the extent of prematurity, such birth defects could include neurological problems (eg. cerebral palsy, apnea of prematurity, retinopathy of prematurity), respiratory problems (eg. respiratory distress syndrome), cardiovascular problems (eg. patent ductus arteriosus), gastrointestinal/metabolic disorders (eg. rickets, inguinal hernia), hematological conditions (eg. jaundice, anemia) and infections (eg. sepsis, UTI). Obviously neonatal mortality is another possible complication of premature birth and generally, the earlier the birth, the more severe the complications. Babies born during the second trimester due to cervical incompetence (as a result of previous cervical dilations associated with the index injury leading to AS and/or surgical correction of AS) are often too young to survive outside the body, and even if they do they will have severe and life long complications.
Effect of IUA during pregnancy: four case reports with different outcomes
It is very important that the uterus is assessed for adhesions after treatment of Asherman’s syndrome before conception is attempted/advised. Adhesions are known to recur in moderate and severe cases, and further surgery may be required. Complications will be increased if pregnancy occurs in the presence of thick adhesions. This is highlighted in the examples from case reports below. Note that the first example is one where the patient underwent endometrial ablation (EA) which is a procedure that mimics very severe AS. It is unclear whether the patient was counseled for the risks of a future pregnancy. Usually both IUA and extensive fibrosis are present. In fibrosis the endometrium is replaced with scar tissue to varying extents (hence it is also known as sclerotic endometrium or ‘unstuck’ Asherman’s syndrome due to the absence of adhesions). This is the most severe form of AS. Fibrosis occurs mainly as a result of thermal energy use in the uterus. Electrosurgery (e.g. resectoscope, laser etc.) also leads to IUA because of damage to the basal endometrium. EA is procedure used to treat abnormally heavy bleeding in which the endometrium is intentionally and irreversibly destroyed using thermal ablation. First reported in 1981, EA has been gaining popularity as a less invasive alternative to hysterectomy. Unfortunately damage may also occur unintentionally when these same instruments are used for other purposes such as the resectioning of uterine fibroids or polyps or the dissection of adhesions during the treatment of Asherman’s syndrome. Instead of having their fertility restored, the patient may end up with more severe adhesions and fibrosis than originally. Therefore mechanical dissection of adhesions may have better outcomes. EA should not be undertaken in women who desire future fertility and they should be informed about potential dangers of pregnancies if they fall pregnant. I have seen doctors on the internet advertizing endometrial ablation reversal in women who wish to conceive after having had the procedure. This practice is highly questionable given the high risk of severe pregnancy complications and the low chance of a live birth after EA. Pregnancy rates following EA are in the vicinity of 0.2-0.7% (3,4) with perinatal mortality reported to be 11.8% (4)
Severe AS from EA and birth defects
1. Mukul and Linn (5) reported amniotic band syndrome (ABS) in a pregnancy following endometrial ablation. The patient had three prior pregnancies and one birth. ABS , also called Amniotic Constriction Band Syndrome, is a set of congenital birth defects believed to be caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero. The patient had undergone rollerball EA 7 years earlier without complications. Ultrasonography at 7 weeks revealed evidence of amniotic band syndrome: synechiae (i.e. IUA) were seen in the midquadrant of the uterus, creating amniotic sheets and bands with small compartments. The entire lower uterine segment was empty except for the right leg and a loop of umbilical cord poking through the lower uterine synechia. The fetus was of normal size but with clubbed feet, a distorted spine, and ventriculomegaly.
The patient underwent preterm labour and membranes ruptured at 26 weeks. A male infant was delivered via emergency C-section. An emergency hysterectomy was performed. The infant’s birth defects were described as follows:
“There were positional deformities in the neck, an asymmetric chest, severe scoliosis confirmed by X-ray, bilateral clubbed feet, and very limited movement of all long extremities consistent with arthrogryposis. The right lower extremity was swollen, cyanotic, denuded of skin, and without perfusion or pulses. Areas of significant necrosis on the posterior thigh of the right lower extremity were noted.”
Prognosis was poor and the parents decided to withdraw ventilation support. The infant died 6 hours after delivery.
One theory on the cause of ABS is that it occurs when the inner membrane (amnion) ruptures without injury to the outer membrane (chorion), exposing the fetus to fibrous tissue (bands) from the ruptured amnion which can entangle body parts, leading to congenital abnormalities. Another theory is that vascular disruption occurs. The latter would explain the presence of cleft lip in ABS cases. Either theory could account for its description in women with severe injury to the endometrium. Both IUA and fibrosis resulting from EA would lead to vascular disruption.
Mild to moderate IUA during pregnancy
In the three examples below, patients developed IUA from uterine curettage (i.e. D&C). One case ended in the term birth of a healthy baby while the other two resulted in congenital abnormalities. It appears that the severity of the adhesions affects outcome.
2. Klatsky et al (3) report of a pregnancy complicated by endometrial scarring which ended in a term birth of a healthy infant. The patient, a 39 year old woman, had a history of D&C for therapeutic abortion followed by three miscarriages, the last of which was completed by D&C. An ultrasound at 19 weeks identified a thick band crossing the lower uterine segment with the placenta inserting alongside it. Mullerian fusion anomalies were ruled out. Doppler flow imaging demonstrated flow along the synechia to the overlying placenta. At 25 weeks the patient passed half a cup of bright red blood. An ultrasound revealed a thinning scar with placenta still implanted on both sides and a small subchorionic hematoma. At 31 weeks ultrasound demonstrated a reduced scar with placenta visible on only one side. The patient presented at term with premature rupture of the membranes and a fetus in breech presentation. She underwent cesarean delivery. No uterine anomalies or adhesions were found, presumabley the thin uterine adhesion was evacuated with the placenta. The infant had no morphological abnormalities.
3. Deering et al (6) report a case of head entrapment of a second twin by intrauterine synechiae leading to long term health complications. The 40 year old patient had a history of two uterine curettages (ie. D&C) , one for first trimester miscarriage and a second for menorrhagia. CVS was undertaken during first trimester revealing normal male karyotypes. Diagnostic hysteroscopy and lysis of adhesions was not performed prior to IVF resulting in a twin pregnancy. She presented at 19 weeks for evaluation due to a shortened cervix and pronounced funneling (symptoms of cervical insufficiency). A McDonald cerclage was placed. Ultrasound examination also revealed a moderate sized uterine synechiae wrapped around the neck and placenta of twin B. Twin B was affected by IUGR, weighing less than the third percentile for gestational age. The development of growth restriction and discordance in twin B is thought to result from the combination of the contracted space available for twin B’s head to grow, the compression of the umbilical cord against the fetal neck by the uterine band, and the implantation of the placenta in an abnormal portion of the uterus with a potentially inadequate blood supply.
Cesarean delivery was undertaken at 26 weeks due to fetal distress of twin B and head entrapment. As seen on ultrasonography a thick uterine band was tightly constricting the neck of twin B. The location of the tissue was consistent with the uterine synechia observed on hysterosalpingogram before IVF. Twin A did well and was discharged from the NICU at 3 months. Twin B remained in the NICU until 5 months of age, at which time he was discharged to a longer-term pediatric care facility for continued care. This case demonstrates that significant uterine synechia might result in intrauterine head entrapment, as well as IUGR.
4. Baumler et al (7) report a case of premature birth of an infant with prolonged pulmonary distress syndrome and severe kyphoscoliosis (90 degrees) in a patient with IUA. The patient was 37 years of age with a history of two first trimester miscarriages and evacuation of retained products of conception (ERPC or D&C). Preterm labor occurred at 28 weeks. Midtrimester 2D, 3D and real-time 4D ultrasound revealed a horizontal miduterine separation in the form of an ‘egg-timer’. The uterine cavity was separated in two superimposed cavities. The fetus and the placenta were located in the upper part of the uterus, and the right arm of the fetus and part of the umbilical cord extended in the lower part of the uterus, through an opening in the separating horizontal membrane. The kyphoscoliosis, thought to be due to severe oligoamnios was managed conservatively.
The mother’s operative hysteroscopy carried out 6 months later confirmed both clinically and histologically the presence of a transversal muscular synechia.
The examples above illustrate the importance of diagnosing and removing IUA prior to IVF or conception. Furthermore, thick adhesions restrict the growth of the uterus, possibly increasing pressure on the cervix and leading to CI or preterm labor. The patient in the example above (6) may not even have needed IVF as her fertility problems may have been due to Asherman’s syndrome which could have been surgically corrected and allowed a better pregnancy outcome. Not only are the chances of pregnancy reduced, the health of the mother and infant are compromised as well with the presence of IUA. It is particularly irresponsible to perform IVF in patients without confirming an architecturally normal uterus. There is unfortunately a tendency for some clinicians to believe that IUA are harmless and asymptomatic (3) but this case shows that even a single thick band can have significant repercussions during pregnancy. As all cases are not treatable, in particular more severe ones where there is a tendency for scars to reform and irreversible fibrosis to occur, prevention of AS wherever possible is the best and easiest strategy available.
REFERENCES
1. Ball RH, Buchmeier SE, Longnecker M. Clinical significance of sonographically detected uterine synechiae in pregnant patients. J Ultrasound Med. 1997 Jul;16(7):465-9. Abstract
2. Klatsky PC, Tran ND, Strachowski L. A pregnancy complicated by endometrial scarring. Fertil Steril. 2009 Jun;91(6):2707-8. Epub 2008 Nov 20 Abstract
3. Cook JR, Seman E. Pregnancy following endometrial ablation: case history and literature review. Obstet Gynecol Surv 2003;58:551– 6. Abstract
4. Pugh CP, Crane JM, Hogan TG. Successful intrauterine pregnancy after endometrial ablation. J Am Assoc Gynecol Laparosc 2000;7:391– 4. Abstract
5 Mukul LV, Linn JG. Pregnancy complicated by uterine synechiae after endometrial ablation. Obstet Gynecol. 2005 May;105(5 Pt 2):1179-82. Abstract
6 Deering SH, Heller J, Winkel C, Landy HJ. Intrauterine head entrapment of a second twin by a uterine synechia. Obstet Gynecol. 2003 Oct;102(4):693-5. Abstract
7 Bäumler M, Faure JM, Couture A, Flunker S, Boulot P. Prenatal 3D ultrasound and MRI assessment of horizontal uterine synechia. Prenat Diagn. 2008 Sep;28(9):874-5.
Wednesday, May 26, 2010
Failed medical management or a failure to comply with accepted guidelines?
Only 4 months after an in utero fetal demise at 14 weeks, I had a first trimester miscarriage at 8 weeks. I had conceived (naturally again) after only a month of trying and the pregnancy was suspected by chance at a follow up for my previous miscarriage only a few days after implantation. I’d had my next ultrasounds at 5 weeks, just under 8 weeks-where a heart rate of 151 bpm was detected- and then at 9 weeks, where there was no longer any cardiac activity.
As if this was not bad enough, I was again faced with how to cope with the physical side of this loss without incurring damage to my previously scarred uterus. Misoprostol was of course my method of choice. I learned that I would have to be admitted as an in-patient according to this hospital’s treatment protocol, although I know that in other countries misoprostol management of first trimester miscarriage (and abortion) are routinely done on an out-patient basis. This of course would increase the cost of the procedure. Once I was admitted, I learned that I would be given the same protocol as for second trimester terminations. This is because the hospital only has protocols in place using misoprostol for late abortions.
I should clarify that in Australia, misoprostol is rarely used for first trimester miscarriage. This was an exception for them and I am relieved that I was not forced into having a D&C which caused this whole debacle to begin with.
What worried me was that the accepted dosage for second trimester terminations (400 mcg every 3 hours up to 5 times) is lower per administration than that recommended for first trimester miscarriage. According to guidelines published in a supplement to the International Journal of Gynecology and Obstetrics (2007, vol. 99) a woman with a first trimester miscarriage should be given 2 doses of 800 mcg of misoprostol (vaginally) 3 hours apart. This is because early in a pregnancy, there are fewer prostaglandin receptors to which misoprostol binds than later in pregnancy.
While I received the same protocol for my previous second trimester miscarriage as for second trimester abortion, the accepted protocols for these two indications are much more similar and was thus it was more effective. However, this dosage is not considered effective for first trimester pregnancy failure and with good reason, as I subsequently found out: it simply does not work. On the first day I received 5 doses but none of them produced contractions that were strong enough to evacuate the uterus. There seemed to be less uterine contractions and bleeding after the first few administrations as though the effects were wearing off. I was given a 12 hour break before starting again. I requested that the drug be given orally instead this time. I had even less of a reaction, not even nausea or diarrhea which are commonly reported side effects of oral misoprostol. The following day, I agreed to hysteroscopic removal with my Asherman’s syndrome specialist.
According to this specialist, my cervix was slightly dilated but not enough for the gestational sac to pass through. The gestational sac had implanted slightly low in the uterine cavity (future placenta previa?), and in the anterior wall, in a region where I’d had scarring from my D&C and adhesions. Tissue obtained during the hysteroscopy did not grow in culture so I was unable to find out the karyotype of the embryo, or subsequently, the gender. It is possible that I miscarried because by chance the embryo implanted in a region where I’d had previous scarring and possible fibrosis, and the blood supply was not sufficient to maintain the pregnancy. If so, this is much more upsetting than if the baby was chromosomally abnormal and would not have survived anyway. I will never know for sure what caused this miscarriage, but an Asherman’s related cause cannot be either confirmed or ruled out.
It is quite possible that I would have required hysteroscopy to remove retained products, as I had previous uterine scarring from Asherman's syndrome, and the embryo also implanted in the area of the previous scarring. However, had I been given the correct dosage, I may not have needed to wait another day to respond to a drug which was given in too low a quantity to be effective anyway.
I noticed that on my hysteroscopic surgery report written under ‘reason for hysteroscopy’ was ‘failed medical management of miscarriage.’ This made me wonder if doctors and nurses would look at my file and incorrectly conclude that misoprostol was an ineffective drug for miscarriage, rather than realizing that the dose I had been given was inappropriate and not officially recommended for my stage of pregnancy. I wonder how many other women who claim their miscarriage management with misoprostol was a ‘failure’ were also given a dose not suited to their gestational age. From a patient perspective, I wonder why it is not possible for my hospital to provide treatment according to published recommendations for that indication (rather than according to a protocol used for another indication ie. second trimester abortion)? What is the logic in applying a protocol which goes against evidence-based medicine? I hope that instead of discouraging doctors, my experience will go towards persuading this hospital to broaden the current protocol so that women with first trimester miscarriage will benefit from misoprostol. For misoprostol to be effective and safe, it needs to be used according to established guidelines which take into account factors such as gestational age and indication.
As if this was not bad enough, I was again faced with how to cope with the physical side of this loss without incurring damage to my previously scarred uterus. Misoprostol was of course my method of choice. I learned that I would have to be admitted as an in-patient according to this hospital’s treatment protocol, although I know that in other countries misoprostol management of first trimester miscarriage (and abortion) are routinely done on an out-patient basis. This of course would increase the cost of the procedure. Once I was admitted, I learned that I would be given the same protocol as for second trimester terminations. This is because the hospital only has protocols in place using misoprostol for late abortions.
I should clarify that in Australia, misoprostol is rarely used for first trimester miscarriage. This was an exception for them and I am relieved that I was not forced into having a D&C which caused this whole debacle to begin with.
What worried me was that the accepted dosage for second trimester terminations (400 mcg every 3 hours up to 5 times) is lower per administration than that recommended for first trimester miscarriage. According to guidelines published in a supplement to the International Journal of Gynecology and Obstetrics (2007, vol. 99) a woman with a first trimester miscarriage should be given 2 doses of 800 mcg of misoprostol (vaginally) 3 hours apart. This is because early in a pregnancy, there are fewer prostaglandin receptors to which misoprostol binds than later in pregnancy.
While I received the same protocol for my previous second trimester miscarriage as for second trimester abortion, the accepted protocols for these two indications are much more similar and was thus it was more effective. However, this dosage is not considered effective for first trimester pregnancy failure and with good reason, as I subsequently found out: it simply does not work. On the first day I received 5 doses but none of them produced contractions that were strong enough to evacuate the uterus. There seemed to be less uterine contractions and bleeding after the first few administrations as though the effects were wearing off. I was given a 12 hour break before starting again. I requested that the drug be given orally instead this time. I had even less of a reaction, not even nausea or diarrhea which are commonly reported side effects of oral misoprostol. The following day, I agreed to hysteroscopic removal with my Asherman’s syndrome specialist.
According to this specialist, my cervix was slightly dilated but not enough for the gestational sac to pass through. The gestational sac had implanted slightly low in the uterine cavity (future placenta previa?), and in the anterior wall, in a region where I’d had scarring from my D&C and adhesions. Tissue obtained during the hysteroscopy did not grow in culture so I was unable to find out the karyotype of the embryo, or subsequently, the gender. It is possible that I miscarried because by chance the embryo implanted in a region where I’d had previous scarring and possible fibrosis, and the blood supply was not sufficient to maintain the pregnancy. If so, this is much more upsetting than if the baby was chromosomally abnormal and would not have survived anyway. I will never know for sure what caused this miscarriage, but an Asherman’s related cause cannot be either confirmed or ruled out.
It is quite possible that I would have required hysteroscopy to remove retained products, as I had previous uterine scarring from Asherman's syndrome, and the embryo also implanted in the area of the previous scarring. However, had I been given the correct dosage, I may not have needed to wait another day to respond to a drug which was given in too low a quantity to be effective anyway.
I noticed that on my hysteroscopic surgery report written under ‘reason for hysteroscopy’ was ‘failed medical management of miscarriage.’ This made me wonder if doctors and nurses would look at my file and incorrectly conclude that misoprostol was an ineffective drug for miscarriage, rather than realizing that the dose I had been given was inappropriate and not officially recommended for my stage of pregnancy. I wonder how many other women who claim their miscarriage management with misoprostol was a ‘failure’ were also given a dose not suited to their gestational age. From a patient perspective, I wonder why it is not possible for my hospital to provide treatment according to published recommendations for that indication (rather than according to a protocol used for another indication ie. second trimester abortion)? What is the logic in applying a protocol which goes against evidence-based medicine? I hope that instead of discouraging doctors, my experience will go towards persuading this hospital to broaden the current protocol so that women with first trimester miscarriage will benefit from misoprostol. For misoprostol to be effective and safe, it needs to be used according to established guidelines which take into account factors such as gestational age and indication.
Monday, May 3, 2010
Ashermans syndrome in the news: The secret syndrome leaving women infertile
A recent article on Asherman’s syndrome (AS) appeared in the UK Daily mirror. It was about Sophie Blake, a TV presenter in the UK, who acquired Asherman’s syndrome as a result of two D&Cs to remove retained placenta after giving birth. It is unfortunate that her situation was not handled differently, as postpartum D&C has been reported to result in Asherman’s syndrome in 25% of cases (1). There are usually alternatives, and in some countries such as Israel, post partum D&C is no longer performed because of AS risks (2).
Toaff and Ballas, 1978
“Puerperal curettage….was discontinued in Israel after publication of Asherman’s observations*”.
*1948!!
Publicity about Asherman’s syndrome is important, and it always helps to have a public figure bring awareness to an overlooked condition. However, according to the article, the moral of the story is to seek early treatment when there is actually no evidence that fertility is more likely to be restored if treatment is sought early. Studies have shown that fertility outcomes are correlated with severity of adhesions (3), however there have been no studies on the effect of length of the condition on fertility. Sometimes damage is too great to be corrected and the uterus will rescar at every attempt to surgically remove adhesions and hormonally stimulate endometrial growth, even when early treatment was commenced. Other times, adhesions are not so severe and treatment after years will result in a live birth. Although treatment by an experienced AS specialist should always be sought, fertility outcome will be dependent most of all on the severity of initial injury (ie. D&C, intrauterine surgery with or without endometritis) which led to the scarring. When too many endometrial cells are removed to allow the endometrium to regenerate, this leads to recurrent adhesions and/or widespread fibrosis. In many cases even some of the underlying myometrium is removed. It is simple, without further progress in treatment strategies, there is nothing that can be done to replenish regenerative tissue that has been removed during curettage or other uterine surgery.
Early treatment does not guarantee success-just as late treatment does not guarantee failure
“Ideally corrective surgery should be performed within six months of the adhesions forming before they get too large”
This suggests that intrauterine adhesions continue to get worse over time, which is not true. Injury results in scarring anywhere in the body, and scarring is not progressive after a certain time point. Adhesions occur when scarring occurs internally and tissues are in direct contact with each other during the healing process. IUA formation is a normal physiological response to trauma-albeit trauma that is usually iatrogenic and should not have occurred in the first place. The consequences of this normal response are pathological because adhesions can lead to infertility, miscarriage and/or obstetric complications when they occur in the uterus. In actuality, IUA formation begins immediately after injury or corrective surgery and is complete by around 6-8 weeks according to Asherman’s syndrome specialists (unfortunately I am unable to find a reference for this, however studies where hysteroscopic followups are performed after D&C mention waiting 6-8 weeks at least). This is even supported in the article:
“I was devastated the scarring had come back so quickly,”
After 8 weeks, IUA do not continue to form/progress. Therefore, someone with stage I AS diagnosed 3 months after surgery will not go on to have stage IV 3 years later, because their adhesions have already fully formed by 8 weeks. There is one study which asserts that women who had early followup compared to late follow up hysteroscopy following adhesiolysis had less severe adhesions, and that early treatment would give a better outcome (4). However, early followup was 2-4 weeks after the initial surgery while late followup was 8-16 months. Thus adhesions may appear to be less ‘severe’ in the early followup group simply because they had not fully formed. The main advantage of early treatment (ie. before 6-8 weeks) is that it makes it easier for the doctor to dissect adhesions and not cause new ones inadvertently. However, in practical terms, it is highly unlikely that women will be diagnosed with AS within 6-8 weeks after a surgery (let alone treated), therefore it is usually applied as a treatment strategy after adhesiolysis instead of a uterine stent (5).
“It makes me seethe because if Asherman’s is caught early it’s totally treatable.”
“It’s treatable in the early stages, but it took two years for me to get a diagnosis.”
It is suggested that had she had surgery sooner, she would have possibly reversed the damage and regained her fertility. This is unlikely. Very severe adhesions tend to recur (3) inspite of surgery or hormone therapy. Early intervention will not make much of a difference because the extent of the initial damage is such that too many regenerative endometrial cells have been removed during the initial trauma.
It has been hypothesized (but not been proven) that the adhesive process can be progressive because adhesions limit uterine muscular activity thereby reducing perfusion of sex steroids to the endometrium which atrophy as the consequence (6). However, endometrial atrophy, which would lead to thin endometrium or fibrosis, is different to IUA. Most current classification systems only take adhesion type and extent into consideration, not fibrosis.
On the other hand, it is possible that someone with moderately severe adhesions which are treatable may develop fibrosis if treatment is not sought for years. Fibrosis would impact on fertility, not by causing IUA, but by limiting blood flow to an area of the uterus.
As one never knows whether their case is severe or not, by all means seek treatment with an AS specialist, but the best prognosis is severity.
Prevalence versus incidence“While the exact number of Asherman’s sufferers is not known, it’s estimated that 5% of D&Cs cause the condition – that’s about 3,000 new cases a year.”
The article confuses the estimated prevalence rate of Asherman’s syndrome (5%) with incidence rate after D&C. The prevalence of AS is 5%, meaning that roughly 1 in 20 women in the general population have AS. This does not however mean that the incidence rate of AS after a D&C is 5%. Incidence is the percentage of women who develop AS from a particular procedure, such as D&C. Studies have reported rates varying between 7.7 and 30% after D&C for miscarriage (7,8,9,10,11), and 25% from D&C for post partum retained placenta 2-4 weeks after delivery (2). The reason the incidence is higher than the prevalence is that not all women will have a miscarriage, and not all women who miscarry will have a missed or incomplete miscarriage or will be treated by D&C. Furthermore, there will be undiagnosed cases of AS (either because the woman does not desire more children or her infertility remains ‘unexplained’), and obviously not every woman in the population will undergo diagnosis for IUA. One should also remember that there are other causes of AS including other intrauterine surgery and genital tuberculosis (12) and these carry different incidence rates too.
It is important to report the correct incidence rate after a procedure such as D&C because this gives women a better idea of risks and helps her to make an informed decision before consenting to the procedure. There are almost always equally effective alternatives to D&C such as drugs or minimally invasive surgery like hysteroscopy which incur no or less damage.
Prevention: more information and accuracy needed
“Doctors are increasingly opting for less-invasive methods including suction or the use of tablets”
It’s unfortunate that the focus of the story was on preventing infertility through early treatment-which is misleading-rather than on promoting alternatives to D&C.
There is one sentence about prevention, and sadly it contains an inaccuracy as well as an omission. Suction D&C has never been proven to prevent AS, let alone reduce the incidence rates of AS:
Chapman and Chapman, 1990: (13)
“It is noteworthy that, of the 11 patients with isthmus stenosis, six of them were attributable to termination of pregnancy, of which all but one had been performed by suction curettage”
Dalton et al, 2006 (14)
“Intrauterine adhesions are a possible complication of office MVA (manual vacuum aspiration), even in the absence of sharp curettage, and should be considered when discussing treatment options for EPF (early pregnancy failure) with patients."
“After 262 office MVAs for first trimester pregnancy losses, we have identified 5 cases of IUAs…”
There is also no guarantee that your doctor will use only suction D&C, as many will use blunt or sharp instruments as well during the same procedure.
The mysterious ‘tablets’ mentioned allude to misoprostol, a prostaglandin E1 analogue which can evacuate the uterus after miscarriage, delivery or during termination, by causing uterine contractions. Referred to as medical management of miscarriage or retained placenta, or medical abortion depending on the situation where it is used, misoprostol is a non-invasive method which has been shown to prevent IUA compared to suction D&C in a clinical trial (7).
Here you can find out more about how misoprostol can prevent AS if you have a miscarriage. It can also prevent recurrence of AS in women who have a miscarriage after having had the condition.
REFERENCES
1. Toaff R, Ballas S (1978). "Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome)". Fertil. Steril. 30 (4): 379–87.
2. Jensen, P.A. and W.B. Stromme, Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol, 1972. 113(2): p. 150-7.
3. Valle RF, and Sciarra JJ (1988). "Intrauterine adhesions: Hystreoscopic diagnosis, classification, treatment and reproductive outcome". . Am J Obstet 158 (6Pt1): 1459–1470.
4. Shokeir, T.A., M. Fawzy, and M. Tatongy, The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications. Arch Gynecol Obstet, 2008. 277(5): p. 423-7.
5. Robinson JK, Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome). Fertil Steril. 2008;90(2):409-14.
6. March CM. (1995). "Intrauterine adhesions". Obstet Gynecol Clin N Am 22: 98–103.
7. Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. (2002). "Intrauterine adhesions after conservative and surgical management of spontaneous abortion". J Am Assoc Gynecol Laparosc. 9 (2): 182–185.
8. Adoni A, Palti Z, Milwidsky A, Dolberg M. (1982). "The incidence of intrauterine adhesions following spontaneous abortion". Int J Fertil. 27 (2): 117–118.
9. Golan, A., et al., Hysteroscopic findings after missed abortion. Fertil Steril, 1992. 58(3): p. 508-10.
10. Romer, T European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 57, Issue 3, December 1994, Pages 171-173
11. Friedler S, Margalioth EJ, Kafka I, Yaffe H. (1993). "Incidence of postabortion intra-uterine adhesions evaluated by hysteroscopy: a prospective study". Hum Reprod 8 (3): 442–444.
12. Kodaman PH, Arici AA. (2007). "Intra-uterine adhesions and fertility outcome: how to optimize success?". Curr Opin Obstet Gynecol 19 (3): 207–214.
13. K Chapman and R Chapman. Asherman's syndrome: a review of the literature, and a husband and wife's 20-year world-wide experience. J R Soc Med. 1990 September; 83(9): 576–580.
14. Dalton VK, Saunders NA, Harris LH, Williams JA, Lebovic DI (2006). "Intrauterine adhesions after manual vacuum aspiration for early pregnancy failure". Fertil. Steril. 85 (6): 1823.e1–3
Toaff and Ballas, 1978
“Puerperal curettage….was discontinued in Israel after publication of Asherman’s observations*”.
*1948!!
Publicity about Asherman’s syndrome is important, and it always helps to have a public figure bring awareness to an overlooked condition. However, according to the article, the moral of the story is to seek early treatment when there is actually no evidence that fertility is more likely to be restored if treatment is sought early. Studies have shown that fertility outcomes are correlated with severity of adhesions (3), however there have been no studies on the effect of length of the condition on fertility. Sometimes damage is too great to be corrected and the uterus will rescar at every attempt to surgically remove adhesions and hormonally stimulate endometrial growth, even when early treatment was commenced. Other times, adhesions are not so severe and treatment after years will result in a live birth. Although treatment by an experienced AS specialist should always be sought, fertility outcome will be dependent most of all on the severity of initial injury (ie. D&C, intrauterine surgery with or without endometritis) which led to the scarring. When too many endometrial cells are removed to allow the endometrium to regenerate, this leads to recurrent adhesions and/or widespread fibrosis. In many cases even some of the underlying myometrium is removed. It is simple, without further progress in treatment strategies, there is nothing that can be done to replenish regenerative tissue that has been removed during curettage or other uterine surgery.
Early treatment does not guarantee success-just as late treatment does not guarantee failure
“Ideally corrective surgery should be performed within six months of the adhesions forming before they get too large”
This suggests that intrauterine adhesions continue to get worse over time, which is not true. Injury results in scarring anywhere in the body, and scarring is not progressive after a certain time point. Adhesions occur when scarring occurs internally and tissues are in direct contact with each other during the healing process. IUA formation is a normal physiological response to trauma-albeit trauma that is usually iatrogenic and should not have occurred in the first place. The consequences of this normal response are pathological because adhesions can lead to infertility, miscarriage and/or obstetric complications when they occur in the uterus. In actuality, IUA formation begins immediately after injury or corrective surgery and is complete by around 6-8 weeks according to Asherman’s syndrome specialists (unfortunately I am unable to find a reference for this, however studies where hysteroscopic followups are performed after D&C mention waiting 6-8 weeks at least). This is even supported in the article:
“I was devastated the scarring had come back so quickly,”
After 8 weeks, IUA do not continue to form/progress. Therefore, someone with stage I AS diagnosed 3 months after surgery will not go on to have stage IV 3 years later, because their adhesions have already fully formed by 8 weeks. There is one study which asserts that women who had early followup compared to late follow up hysteroscopy following adhesiolysis had less severe adhesions, and that early treatment would give a better outcome (4). However, early followup was 2-4 weeks after the initial surgery while late followup was 8-16 months. Thus adhesions may appear to be less ‘severe’ in the early followup group simply because they had not fully formed. The main advantage of early treatment (ie. before 6-8 weeks) is that it makes it easier for the doctor to dissect adhesions and not cause new ones inadvertently. However, in practical terms, it is highly unlikely that women will be diagnosed with AS within 6-8 weeks after a surgery (let alone treated), therefore it is usually applied as a treatment strategy after adhesiolysis instead of a uterine stent (5).
“It makes me seethe because if Asherman’s is caught early it’s totally treatable.”
“It’s treatable in the early stages, but it took two years for me to get a diagnosis.”
It is suggested that had she had surgery sooner, she would have possibly reversed the damage and regained her fertility. This is unlikely. Very severe adhesions tend to recur (3) inspite of surgery or hormone therapy. Early intervention will not make much of a difference because the extent of the initial damage is such that too many regenerative endometrial cells have been removed during the initial trauma.
It has been hypothesized (but not been proven) that the adhesive process can be progressive because adhesions limit uterine muscular activity thereby reducing perfusion of sex steroids to the endometrium which atrophy as the consequence (6). However, endometrial atrophy, which would lead to thin endometrium or fibrosis, is different to IUA. Most current classification systems only take adhesion type and extent into consideration, not fibrosis.
On the other hand, it is possible that someone with moderately severe adhesions which are treatable may develop fibrosis if treatment is not sought for years. Fibrosis would impact on fertility, not by causing IUA, but by limiting blood flow to an area of the uterus.
As one never knows whether their case is severe or not, by all means seek treatment with an AS specialist, but the best prognosis is severity.
Prevalence versus incidence“While the exact number of Asherman’s sufferers is not known, it’s estimated that 5% of D&Cs cause the condition – that’s about 3,000 new cases a year.”
The article confuses the estimated prevalence rate of Asherman’s syndrome (5%) with incidence rate after D&C. The prevalence of AS is 5%, meaning that roughly 1 in 20 women in the general population have AS. This does not however mean that the incidence rate of AS after a D&C is 5%. Incidence is the percentage of women who develop AS from a particular procedure, such as D&C. Studies have reported rates varying between 7.7 and 30% after D&C for miscarriage (7,8,9,10,11), and 25% from D&C for post partum retained placenta 2-4 weeks after delivery (2). The reason the incidence is higher than the prevalence is that not all women will have a miscarriage, and not all women who miscarry will have a missed or incomplete miscarriage or will be treated by D&C. Furthermore, there will be undiagnosed cases of AS (either because the woman does not desire more children or her infertility remains ‘unexplained’), and obviously not every woman in the population will undergo diagnosis for IUA. One should also remember that there are other causes of AS including other intrauterine surgery and genital tuberculosis (12) and these carry different incidence rates too.
It is important to report the correct incidence rate after a procedure such as D&C because this gives women a better idea of risks and helps her to make an informed decision before consenting to the procedure. There are almost always equally effective alternatives to D&C such as drugs or minimally invasive surgery like hysteroscopy which incur no or less damage.
Prevention: more information and accuracy needed
“Doctors are increasingly opting for less-invasive methods including suction or the use of tablets”
It’s unfortunate that the focus of the story was on preventing infertility through early treatment-which is misleading-rather than on promoting alternatives to D&C.
There is one sentence about prevention, and sadly it contains an inaccuracy as well as an omission. Suction D&C has never been proven to prevent AS, let alone reduce the incidence rates of AS:
Chapman and Chapman, 1990: (13)
“It is noteworthy that, of the 11 patients with isthmus stenosis, six of them were attributable to termination of pregnancy, of which all but one had been performed by suction curettage”
Dalton et al, 2006 (14)
“Intrauterine adhesions are a possible complication of office MVA (manual vacuum aspiration), even in the absence of sharp curettage, and should be considered when discussing treatment options for EPF (early pregnancy failure) with patients."
“After 262 office MVAs for first trimester pregnancy losses, we have identified 5 cases of IUAs…”
There is also no guarantee that your doctor will use only suction D&C, as many will use blunt or sharp instruments as well during the same procedure.
The mysterious ‘tablets’ mentioned allude to misoprostol, a prostaglandin E1 analogue which can evacuate the uterus after miscarriage, delivery or during termination, by causing uterine contractions. Referred to as medical management of miscarriage or retained placenta, or medical abortion depending on the situation where it is used, misoprostol is a non-invasive method which has been shown to prevent IUA compared to suction D&C in a clinical trial (7).
Here you can find out more about how misoprostol can prevent AS if you have a miscarriage. It can also prevent recurrence of AS in women who have a miscarriage after having had the condition.
REFERENCES
1. Toaff R, Ballas S (1978). "Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome)". Fertil. Steril. 30 (4): 379–87.
2. Jensen, P.A. and W.B. Stromme, Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol, 1972. 113(2): p. 150-7.
3. Valle RF, and Sciarra JJ (1988). "Intrauterine adhesions: Hystreoscopic diagnosis, classification, treatment and reproductive outcome". . Am J Obstet 158 (6Pt1): 1459–1470.
4. Shokeir, T.A., M. Fawzy, and M. Tatongy, The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications. Arch Gynecol Obstet, 2008. 277(5): p. 423-7.
5. Robinson JK, Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome). Fertil Steril. 2008;90(2):409-14.
6. March CM. (1995). "Intrauterine adhesions". Obstet Gynecol Clin N Am 22: 98–103.
7. Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. (2002). "Intrauterine adhesions after conservative and surgical management of spontaneous abortion". J Am Assoc Gynecol Laparosc. 9 (2): 182–185.
8. Adoni A, Palti Z, Milwidsky A, Dolberg M. (1982). "The incidence of intrauterine adhesions following spontaneous abortion". Int J Fertil. 27 (2): 117–118.
9. Golan, A., et al., Hysteroscopic findings after missed abortion. Fertil Steril, 1992. 58(3): p. 508-10.
10. Romer, T European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 57, Issue 3, December 1994, Pages 171-173
11. Friedler S, Margalioth EJ, Kafka I, Yaffe H. (1993). "Incidence of postabortion intra-uterine adhesions evaluated by hysteroscopy: a prospective study". Hum Reprod 8 (3): 442–444.
12. Kodaman PH, Arici AA. (2007). "Intra-uterine adhesions and fertility outcome: how to optimize success?". Curr Opin Obstet Gynecol 19 (3): 207–214.
13. K Chapman and R Chapman. Asherman's syndrome: a review of the literature, and a husband and wife's 20-year world-wide experience. J R Soc Med. 1990 September; 83(9): 576–580.
14. Dalton VK, Saunders NA, Harris LH, Williams JA, Lebovic DI (2006). "Intrauterine adhesions after manual vacuum aspiration for early pregnancy failure". Fertil. Steril. 85 (6): 1823.e1–3
Wednesday, April 21, 2010
The DO’s and DON’T's (and maybe’s) of Managing Intrauterine Adhesions.
Based on: AAGL: Practice Report: Practice Guidelines for Management of Intrauterine Synechiae, The Journal of Minimally Invasive Gynecology Vol. 17, No.1 2010.
Practice committee members:
Malcolm Munro MD, FRCS(C), FACOG
Rafaele F.Valle,MD
Jason A. Abbott, PhD,FRANZCOG,MRCOG
Angus J.M. Thompson, MRCOG
Keith B. Isaacson, MD
Adolf Gallinat, MD
Volker R. Jacobs, MD, PhD, MBA
Fred M. Howard MD
Andrew I. Sokol, MD
Linda D. Bradley, MD
Recently, the Practice Committee of the AAGL developed guidelines for the management of intrauterine adhesions (IUA), published in the Journal of Minimally Invasive Gynecology (2010). This is a welcome initiative, and long-awaited, with over one century passing since the first description of Asherman’s syndrome in the literature (1). Although these guidelines were based on studies published in peer-reviewed medical journals, there are limitations and room for more specific guidelines, as the authors themselves acknowledge, due to a lack of comparative studies and rigorous medical evidence from randomized controlled trials (RCTs). For example, studies were conducted using different surgical modalities, surgical tools, adjunctive therapies, and hormone therapy protocols. Many studies are also old and/or conducted retrospectively. One of the difficulties of studying IUA is that it is under diagnosed so that many women may not realize they have it. This results in a small sample size for studies, especially when patient treatment is spread between different centers. Additionally, the skills of the surgeon are important in influencing outcome which makes comparisons between different studies difficult. Consequently, drawing meaningful conclusions on treatment is problematic. To circumvent these shortcomings, the authors classified data based on the highest level of evidence found in the data and graded them according to a system outlined by the US Preventive Services Task Force. In most cases the evidence is based primarily on consensus and expert opinion (Level C). Hopefully trials will be forthcoming which meet today’s strict standards of clinical research, and recommendations which are stronger and more specific will result from them.
The goal of IUA management is to restore the volume and architecture of the uterine cavity and its communication with the fallopian tubes and cervical canal by removing IUA, preventing their recurrence and regenerating deficient endometrial growth.
Below is a summary of the recommendations of the article. My additional comments are in blue font.DIAGNOSISHysteroscopy is the most accurate method for diagnosis of IUA and should be chosen over HSG and SHG (although the latter are reasonable alternatives if hysteroscopy is not available).
(Grade B)
CLASSIFICATION
Although there are several classification systems, none is considered superior over the other, probably reflecting inadequacies in all current systems. (Grade C)
An accurate and universal classification system for IUA is important for enabling the comparison of studies and providing prognostic indicators of fertility outcome. (Grade B)
TREATMENT
DO's:
Only expert hysteroscopists familiar with IUA treatment should attempt to treat extensive or dense adhesions. (Level C)(Surgeons who are inexperienced may inadvertantly cause further irreparable damage).
Direct visualization of the uterus during hysteroscopic lysis of adhesions using a tool for dissection is the treatment of choice for IUA which underlies infertility, recurrent pregnancy loss, pain or other related symptoms. (Level C).
In some women expectant management may be acceptable. (Level C)
(ie. if adhesions are thin and filmy and/or cover a small surface area treatment benefits may not outweigh treatment risks).
Estrogen therapy with or without progestin may reduce reformation of IUAs. (Level B)(Estrogen therapy dose and length will depend on severity. See also Recommendations for Future Research).
MAYBE's:
Gel barriers such as hyaluronic acid and auto-cross-linked hyaluronic acid gel may reduce IUA recurrence follow surgical correction, however there is not enough data on pregnancy outcomes following their use, so should not be used without more rigorous trials. (Level A)
(Potential problems with gel barriers are that they are difficult to keep in place, become less viscous at body temperature, draining out of the uterus. See also Recommendations for Future Research).
Foley catheter or IUD should not be used routinely after corrective surgery without further data from trials supporting their benefit. This is because they may increase the risk for infection. (Level C)
(There have been reports of IUDs puncturing the uterus. Also, some doctors also believe that intrauterine pressure from balloons can hinder endometrial regeneration. However, both the Foley catheter and the Cook stent-which curiously was not mentioned in the article-have been used successfully (2)).
Supporting or refuting the use of prophylactic antibiotics before, during or after surgical adhesiolysis. (Level C)
(However, antibiotic prophylaxis should be used in the case of barriers, as a foreign object inside the uterus increases the risk of infection. See also Recommendations for Future Research).
Medications to improve blood flow to the endometrium should be used only after being supported by rigorous research. (Level C)(These include low-dose aspirin, Coenzyme Q-10, vitamin E, and Sildenafil citrate.ie. Viagra, and even herbal remedies such as raspberry leaf tea).
Prevention of complications (eg. perforation) or improved outcomes with the use of external imaging techniques or laparoscopy, however these techniques may have advantages in case perforation does occur. (Level B)(Another advantage is that laparoscopy allows the surgeon to view the pelvic cavity where there may be endometriosis (3), especially in the more severe cases where laparoscopy is often used).
DON’T's:
There is no evidence to support blind D&C or blind cervical probing in the treatment of IUA (Level C)(The authors state that D&C should not be used because it does not permit accurate diagnosis and classification. The bigger concern should be that blind curettage may cause further and irreversible damage and is the underlying cause of most IUA (4)).
Copper (inflammatory), progestin-releasing (suppress endometrium) and T-shaped IUDs (small surface area) should not be used after adhesiolysis. (Level C)
Laparotomy should be considered as a last resort (eg. when hysteroscopic surgery fails) (Level C)
Electrosurgery/laser: There is some disagreement over which tools are best suited for adhesiolysis. Some surgeons prefer to use microscissors and stress that thermal energy tools offer no advantage over scissor dissection with regards to either speed or hemostasis (2). Furthermore, these modalities (including resectoscope, Nd:YAG laser, monopolar/bipolar electrode) deliver energy that can cause injury to surrounding tissues and therefore some believe it is prudent to avoid them for the treatment of IUA (2). Indeed, electrosurgical tools are normally used for endometrial ablation which burns away endometrium and intentionally induces Asherman’s syndrome in women with excessive bleeding. However, other doctors claim that in experienced hands these tools are safe. Which ever the case, this is an issue which probably needs to be further examined to refute any safety concerns.POSTOPERATIVE ASSESSMENT:Follow-up evaluation of the uterine cavity is recommended after treatment of IUA. (Level B).(This is an important factor in determining outcome as adhesions may reform and further surgery may be needed. If a pregnancy occurs in a uterus with IUA, there is a higher likelihood of infertility, miscarriage and pregnancy complications (5). Patients should undergo either HSG, SHG, or in-office hysteroscopy (with as narrow cervical dilation as possible) in order to verify the uterine cavity is free of adhesions. A mid-cycle scan should also be used to measure the endometrial thickness at ovulation. Ideally this should measure 7-8 mm for implantation to be successful. Some women with corrected IUA have thin endometrium which may require hormone treatment to thicken. If adhesions blocking the ostium are present, natural conception is not possible and IVF will be recommended).
RECOMMENDATIONS FOR FUTURE RESEARCH:
1. Prospective trials on the effect of intraoperative and postoperative antibiotic prophylaxis on surgical and fertility outcome.(I don’t know of doctors who do not use antibiotics during or after operative hysteroscopy. Also, the article states: “…it has been proposed that infection may be a primary cause of IUAs…” Antibiotic prophylaxis is wise for preventing infections whether or not they lead to IUA. However, at this stage, there is actually no evidence to support that most IUAs result from infection, whether frank or subclinical. In fact, there is limited evidence to the contrary (6,7). Also see The subclinical infection myth).2. Prospective trials of adjunctive hormone therapy efficacy with respect to surgical and fertility outcome.(The optimum dosage of estrogen (E2 with or without progestin, P4) and length of treatment have not been studied. Progynova (Estradiol valerate) a synthetic version of a naturally occurring estrogen or Premarin, a combination of around 11 conjugated equine estrogens extracted from pregnant mare urine, are usually used. These compounds have not been compared to each other in trials).
3. Prospective trials of barrier method (IUD, Foley catheter and gel adhesion barriers) efficacy with respect to surgical and fertility outcome.
(Presumably the Cook stent, which is used by some doctors (2), should also be included in trials. Regarding the use of gel adhesion barriers which are potentially the least invasive and risky type of barrier, one questions why there is not more research on their use to prevent IUA from occurring in the first place. If gel barriers are therapeutic for reducing IUA reformation after hysteroscopic adhesiolysis perhaps their use after D&C and other primary intrauterine surgery would reduce the incidence of IUA. There is so far only one study and results show only 10% of women who received Seprafilm after curettage for miscarriage developed IUA vs 50% amongst controls (8)).
4. Stem cells for future treatment: As discussed in a previous blog, some cases are currently not treatable because the extent of damage to the basal endometrium (sometimes curettage even removes part of the underlying myometrium) from which the functional layer regenerates. This leads to persistently thin endometrium or reformation of IUA after corrective surgery and excludes the possibility of carrying a pregnancy. Surrogacy is the only option in such cases. However Dr Chaitanya Nagori and Dr Sonal Panchal of Nagori Institute of Infertility in India claim to have used stem cell technology to thicken the endometrium in women who underwent excessive ‘cleaning’ up of the uterus (ie. a euphemism for D&C), although they do not mention the presence of IUA. The process involved isolating adult stem cells from the bone marrow of the patient, transplanting the purified stem cells into the patient’s uterine cavity under transvaginal sonographic guidance, and stimulating the production of endometrial angiogenic stem cells by administering estrogen before IVF treatment. Using this technique they reportedly were able to increase ‘negligible’ endometrial growth to 6mm three months after the transfer and estrogen therapy. Although they assert that IVF drugs alone did not increase the patient’s endometrial measurement, it remains to be proven whether this effect is due to the post-transplant estrogen treatment or from the stem cell therapy. Nonetheless, the concept of using stem cells for tissue repair in the uterus is intriguing, and possibly the best hope in future for very severe cases of IUA (uterine transplant is another future possibility). This could be more convincing if recurrent IUA was prevented with stem cells following hysteroscopic adhesiolysis. Definitive proof would be obtained if the stem cells and their progeny were biochemically labeled so as to be identifiable from the original tissue. This could be done in animal studies, for example. The great advantage of stem cells is that they have the capacity to differentiate into a range of cells that are necessary to rebuild a normal uterus, from myometrium and endometrium to the blood vessels which supply them with blood and hormones. Furthermore, as the stem cells are derived from the patient’s own bone marrow ie. autologous adult stem cells, there is no risk of either rejection or ethical controversy (as with embryonic stem cells). Unfortunately at this stage there are no published studies on this treatment.
REFERENCES
1. Fritsch H, Ein Fall von volligem Schwaund der Gebormutterhohle nach Auskratzung. Zentralbl Gynaekol 1894; 18:1337-1342.
2. March, CM; Miller, CE. Hysteroscopic lysis of intrauterine adhesions. Ob.Gyn. News 2006; 41(23):36-37. Abstract
3. Palter. SF, High Rates of Endometriosis in Patients With Intrauterine Synechiae (Asherman's Syndrome). Fertility and Sterility 2005; 86 (null):S471-S471. Link
4. Palter S, Spyrou P. Asherman’s syndrome: Etiologic factors, patterns of pregnancy loss, and treatment results. Results from an international registry. Fertility and Sterility 2003; 80(3):36-7. Link
5. March CM. Intrauterine adhesions. Obstet Gynecol Clin N Am 1995;22(3):491-505. Abstract
6. Jensen, P.A. and Stromme, W.B. Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol 1972; 113: 150–4.
7. Polishuk, SO Anteby and D Weinstein, Puerperal endometritis and intrauterine adhesions, Int Surg 1975;60:418–420. Abstract
8. Tsapanos VS, Stathopoulou LP, Papathanassopoulou VS, Tzingounis VA. The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. Biomed Material Res. 2002;63:10-14. Abstract
Related Links:Good news: Grow endometrium by stem cells. (Times of India)
Recommendation Grading:
Level A: Recommendations are based on good and consistent scientific evidence.
Level B: Recommendations are based on limited or incomsistent scientific evidence.
Level C: Recommendations are based primarily on consensus and expert opinion.
Practice committee members:
Malcolm Munro MD, FRCS(C), FACOG
Rafaele F.Valle,MD
Jason A. Abbott, PhD,FRANZCOG,MRCOG
Angus J.M. Thompson, MRCOG
Keith B. Isaacson, MD
Adolf Gallinat, MD
Volker R. Jacobs, MD, PhD, MBA
Fred M. Howard MD
Andrew I. Sokol, MD
Linda D. Bradley, MD
Recently, the Practice Committee of the AAGL developed guidelines for the management of intrauterine adhesions (IUA), published in the Journal of Minimally Invasive Gynecology (2010). This is a welcome initiative, and long-awaited, with over one century passing since the first description of Asherman’s syndrome in the literature (1). Although these guidelines were based on studies published in peer-reviewed medical journals, there are limitations and room for more specific guidelines, as the authors themselves acknowledge, due to a lack of comparative studies and rigorous medical evidence from randomized controlled trials (RCTs). For example, studies were conducted using different surgical modalities, surgical tools, adjunctive therapies, and hormone therapy protocols. Many studies are also old and/or conducted retrospectively. One of the difficulties of studying IUA is that it is under diagnosed so that many women may not realize they have it. This results in a small sample size for studies, especially when patient treatment is spread between different centers. Additionally, the skills of the surgeon are important in influencing outcome which makes comparisons between different studies difficult. Consequently, drawing meaningful conclusions on treatment is problematic. To circumvent these shortcomings, the authors classified data based on the highest level of evidence found in the data and graded them according to a system outlined by the US Preventive Services Task Force. In most cases the evidence is based primarily on consensus and expert opinion (Level C). Hopefully trials will be forthcoming which meet today’s strict standards of clinical research, and recommendations which are stronger and more specific will result from them.
The goal of IUA management is to restore the volume and architecture of the uterine cavity and its communication with the fallopian tubes and cervical canal by removing IUA, preventing their recurrence and regenerating deficient endometrial growth.
Below is a summary of the recommendations of the article. My additional comments are in blue font.DIAGNOSISHysteroscopy is the most accurate method for diagnosis of IUA and should be chosen over HSG and SHG (although the latter are reasonable alternatives if hysteroscopy is not available).
(Grade B)
CLASSIFICATION
Although there are several classification systems, none is considered superior over the other, probably reflecting inadequacies in all current systems. (Grade C)
An accurate and universal classification system for IUA is important for enabling the comparison of studies and providing prognostic indicators of fertility outcome. (Grade B)
TREATMENT
DO's:
Only expert hysteroscopists familiar with IUA treatment should attempt to treat extensive or dense adhesions. (Level C)(Surgeons who are inexperienced may inadvertantly cause further irreparable damage).
Direct visualization of the uterus during hysteroscopic lysis of adhesions using a tool for dissection is the treatment of choice for IUA which underlies infertility, recurrent pregnancy loss, pain or other related symptoms. (Level C).
In some women expectant management may be acceptable. (Level C)
(ie. if adhesions are thin and filmy and/or cover a small surface area treatment benefits may not outweigh treatment risks).
Estrogen therapy with or without progestin may reduce reformation of IUAs. (Level B)(Estrogen therapy dose and length will depend on severity. See also Recommendations for Future Research).
MAYBE's:
Gel barriers such as hyaluronic acid and auto-cross-linked hyaluronic acid gel may reduce IUA recurrence follow surgical correction, however there is not enough data on pregnancy outcomes following their use, so should not be used without more rigorous trials. (Level A)
(Potential problems with gel barriers are that they are difficult to keep in place, become less viscous at body temperature, draining out of the uterus. See also Recommendations for Future Research).
Foley catheter or IUD should not be used routinely after corrective surgery without further data from trials supporting their benefit. This is because they may increase the risk for infection. (Level C)
(There have been reports of IUDs puncturing the uterus. Also, some doctors also believe that intrauterine pressure from balloons can hinder endometrial regeneration. However, both the Foley catheter and the Cook stent-which curiously was not mentioned in the article-have been used successfully (2)).
Supporting or refuting the use of prophylactic antibiotics before, during or after surgical adhesiolysis. (Level C)
(However, antibiotic prophylaxis should be used in the case of barriers, as a foreign object inside the uterus increases the risk of infection. See also Recommendations for Future Research).
Medications to improve blood flow to the endometrium should be used only after being supported by rigorous research. (Level C)(These include low-dose aspirin, Coenzyme Q-10, vitamin E, and Sildenafil citrate.ie. Viagra, and even herbal remedies such as raspberry leaf tea).
Prevention of complications (eg. perforation) or improved outcomes with the use of external imaging techniques or laparoscopy, however these techniques may have advantages in case perforation does occur. (Level B)(Another advantage is that laparoscopy allows the surgeon to view the pelvic cavity where there may be endometriosis (3), especially in the more severe cases where laparoscopy is often used).
DON’T's:
There is no evidence to support blind D&C or blind cervical probing in the treatment of IUA (Level C)(The authors state that D&C should not be used because it does not permit accurate diagnosis and classification. The bigger concern should be that blind curettage may cause further and irreversible damage and is the underlying cause of most IUA (4)).
Copper (inflammatory), progestin-releasing (suppress endometrium) and T-shaped IUDs (small surface area) should not be used after adhesiolysis. (Level C)
Laparotomy should be considered as a last resort (eg. when hysteroscopic surgery fails) (Level C)
Electrosurgery/laser: There is some disagreement over which tools are best suited for adhesiolysis. Some surgeons prefer to use microscissors and stress that thermal energy tools offer no advantage over scissor dissection with regards to either speed or hemostasis (2). Furthermore, these modalities (including resectoscope, Nd:YAG laser, monopolar/bipolar electrode) deliver energy that can cause injury to surrounding tissues and therefore some believe it is prudent to avoid them for the treatment of IUA (2). Indeed, electrosurgical tools are normally used for endometrial ablation which burns away endometrium and intentionally induces Asherman’s syndrome in women with excessive bleeding. However, other doctors claim that in experienced hands these tools are safe. Which ever the case, this is an issue which probably needs to be further examined to refute any safety concerns.POSTOPERATIVE ASSESSMENT:Follow-up evaluation of the uterine cavity is recommended after treatment of IUA. (Level B).(This is an important factor in determining outcome as adhesions may reform and further surgery may be needed. If a pregnancy occurs in a uterus with IUA, there is a higher likelihood of infertility, miscarriage and pregnancy complications (5). Patients should undergo either HSG, SHG, or in-office hysteroscopy (with as narrow cervical dilation as possible) in order to verify the uterine cavity is free of adhesions. A mid-cycle scan should also be used to measure the endometrial thickness at ovulation. Ideally this should measure 7-8 mm for implantation to be successful. Some women with corrected IUA have thin endometrium which may require hormone treatment to thicken. If adhesions blocking the ostium are present, natural conception is not possible and IVF will be recommended).
RECOMMENDATIONS FOR FUTURE RESEARCH:
1. Prospective trials on the effect of intraoperative and postoperative antibiotic prophylaxis on surgical and fertility outcome.(I don’t know of doctors who do not use antibiotics during or after operative hysteroscopy. Also, the article states: “…it has been proposed that infection may be a primary cause of IUAs…” Antibiotic prophylaxis is wise for preventing infections whether or not they lead to IUA. However, at this stage, there is actually no evidence to support that most IUAs result from infection, whether frank or subclinical. In fact, there is limited evidence to the contrary (6,7). Also see The subclinical infection myth).2. Prospective trials of adjunctive hormone therapy efficacy with respect to surgical and fertility outcome.(The optimum dosage of estrogen (E2 with or without progestin, P4) and length of treatment have not been studied. Progynova (Estradiol valerate) a synthetic version of a naturally occurring estrogen or Premarin, a combination of around 11 conjugated equine estrogens extracted from pregnant mare urine, are usually used. These compounds have not been compared to each other in trials).
3. Prospective trials of barrier method (IUD, Foley catheter and gel adhesion barriers) efficacy with respect to surgical and fertility outcome.
(Presumably the Cook stent, which is used by some doctors (2), should also be included in trials. Regarding the use of gel adhesion barriers which are potentially the least invasive and risky type of barrier, one questions why there is not more research on their use to prevent IUA from occurring in the first place. If gel barriers are therapeutic for reducing IUA reformation after hysteroscopic adhesiolysis perhaps their use after D&C and other primary intrauterine surgery would reduce the incidence of IUA. There is so far only one study and results show only 10% of women who received Seprafilm after curettage for miscarriage developed IUA vs 50% amongst controls (8)).
4. Stem cells for future treatment: As discussed in a previous blog, some cases are currently not treatable because the extent of damage to the basal endometrium (sometimes curettage even removes part of the underlying myometrium) from which the functional layer regenerates. This leads to persistently thin endometrium or reformation of IUA after corrective surgery and excludes the possibility of carrying a pregnancy. Surrogacy is the only option in such cases. However Dr Chaitanya Nagori and Dr Sonal Panchal of Nagori Institute of Infertility in India claim to have used stem cell technology to thicken the endometrium in women who underwent excessive ‘cleaning’ up of the uterus (ie. a euphemism for D&C), although they do not mention the presence of IUA. The process involved isolating adult stem cells from the bone marrow of the patient, transplanting the purified stem cells into the patient’s uterine cavity under transvaginal sonographic guidance, and stimulating the production of endometrial angiogenic stem cells by administering estrogen before IVF treatment. Using this technique they reportedly were able to increase ‘negligible’ endometrial growth to 6mm three months after the transfer and estrogen therapy. Although they assert that IVF drugs alone did not increase the patient’s endometrial measurement, it remains to be proven whether this effect is due to the post-transplant estrogen treatment or from the stem cell therapy. Nonetheless, the concept of using stem cells for tissue repair in the uterus is intriguing, and possibly the best hope in future for very severe cases of IUA (uterine transplant is another future possibility). This could be more convincing if recurrent IUA was prevented with stem cells following hysteroscopic adhesiolysis. Definitive proof would be obtained if the stem cells and their progeny were biochemically labeled so as to be identifiable from the original tissue. This could be done in animal studies, for example. The great advantage of stem cells is that they have the capacity to differentiate into a range of cells that are necessary to rebuild a normal uterus, from myometrium and endometrium to the blood vessels which supply them with blood and hormones. Furthermore, as the stem cells are derived from the patient’s own bone marrow ie. autologous adult stem cells, there is no risk of either rejection or ethical controversy (as with embryonic stem cells). Unfortunately at this stage there are no published studies on this treatment.
REFERENCES
1. Fritsch H, Ein Fall von volligem Schwaund der Gebormutterhohle nach Auskratzung. Zentralbl Gynaekol 1894; 18:1337-1342.
2. March, CM; Miller, CE. Hysteroscopic lysis of intrauterine adhesions. Ob.Gyn. News 2006; 41(23):36-37. Abstract
3. Palter. SF, High Rates of Endometriosis in Patients With Intrauterine Synechiae (Asherman's Syndrome). Fertility and Sterility 2005; 86 (null):S471-S471. Link
4. Palter S, Spyrou P. Asherman’s syndrome: Etiologic factors, patterns of pregnancy loss, and treatment results. Results from an international registry. Fertility and Sterility 2003; 80(3):36-7. Link
5. March CM. Intrauterine adhesions. Obstet Gynecol Clin N Am 1995;22(3):491-505. Abstract
6. Jensen, P.A. and Stromme, W.B. Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol 1972; 113: 150–4.
7. Polishuk, SO Anteby and D Weinstein, Puerperal endometritis and intrauterine adhesions, Int Surg 1975;60:418–420. Abstract
8. Tsapanos VS, Stathopoulou LP, Papathanassopoulou VS, Tzingounis VA. The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. Biomed Material Res. 2002;63:10-14. Abstract
Related Links:Good news: Grow endometrium by stem cells. (Times of India)
Recommendation Grading:
Level A: Recommendations are based on good and consistent scientific evidence.
Level B: Recommendations are based on limited or incomsistent scientific evidence.
Level C: Recommendations are based primarily on consensus and expert opinion.
Thursday, April 8, 2010
Complications in post Ashermans syndrome Pregnancies (Part II)
Continued from Part I
Click here for pregnancies in the presence of intrauterine adhesions (synechiae).
Cervical incompetence/insufficiency
Cervical incompetence or insufficiency is when the involuntary muscle of the cervix is structurally weak and unable to sustain the weight of the growing fetus. Effacement (shortening and thinning of the cervical walls) occurs prematurely and in the absence of contractions, resulting in bulging of the amniotic membranes, leading to rupture and premature birth. This often occurs during the second trimester before the fetus is able to survive outside the uterus. Cervical incompetence is associated with AS although it is thought to result not from having had scarring but rather as a consequence of frequent dilations of the cervix during procedures such as D&C and hysteroscopy- which itself is used to correct AS. The less widely and less often the cervix is dilated, the better, as frequent dilations of over 8mm put women at an increased risk of cervical incompetence in subsequent pregnancies. In order to monitor for CI, transvaginal ultrasound measurements of the cervix should be undertaken beginning during second trimester at around 16 weeks. Women cannot sense or predict its occurrence and it is also difficult for Obgyns to predict and prevent even with close monitoring as it may have a very sudden onset. It is thought that the increased rate of second trimester pregnancy loss in women with past AS is due to CI. In one study, 3 of 15 pregnancies (20%) were complicated with second trimester fetal loss (9) probably caused by CI. Cervical incompetence may be managed with bed rest and cervical cerclage (9). Cerclage is a cervical stitch sewn to prevent the cervix from opening and it may be placed vaginally or abdominally. Cerclage is a controversial obstetric procedure and studies are continuing to investigate how effective it is. Therapeutic cerclage is used when the cervix is showing signs that it is dangerously shortened ( under 2cm) or funneling, however it is not always effective at this stage and pregnancy loss may still occur. ‘Prophylactic’ cerclages are usually indicated in women with a past history of CI ie. whom have already experienced CI in a previous pregnancy. Because cerclage itself carries the risk of infection, inflammation, and rupture of membranes, it is not routinely recommended in women with past AS. Instead, monitoring of cervical length and therapeutic cerclage if needed is recommended. Interestingly, a study on women with short cervix during pregnancy (under 1.5 cm measured around 22 weeks of gestation) found that progesterone supplementation reduced spontaneous delivery before 34 weeks compared to placebo (25).
Possibilities for prevention of CI include the reduction/replacement of D&C with drugs or expectant management, the use of smaller instruments necessitating less dilation during hysteroscopic surgery (11), and the use of misoprostol for cervical priming (instead of mechanical force for dilation).
IUGR
IUGR (intrauterine growth restriction, or fetal growth restriction) refers to a condition where the fetus is smaller than expected for its gestational age (less than the 10th percentile). Newborns with IUGR are termed small for gestational age (SGA). IUGR is caused by a reduction in oxygen and nutrients delivered to the growing fetus due to a lack of adequate blood flow to the placenta. As the endometrium of women with past AS may be damaged, blood flow to the uterus and placenta may be suboptimal, leading to poor placenta perfusion. There are also other causes of IUGR including high blood pressure, diabetes, cigarette smoking, substance abuse, malnutrition, and kidney disease. A lack of oxygen reduces the fetal heart rate and puts the life of the fetus at great risk. IUGR may be early or late-onset, however the earlier the onset, the greater the risks. Risks include premature delivery, stillbirth, and long-term growth problems in children. Diagnosis is made by ultrasound measurements of the fetal size and fetal weight estimation. Doppler flow studies can be used in conjunction with ultrasound to measure the quantity and velocity of blood flow in the fetal brain and umbilical cord. IUGR cannot be predicted or reversed, however its possible presence should be closely monitored in women with a past history of AS. Placenta previa, another potential complication of AS, is also associated with IUGR. Bed rest and increased maternal nutrition may help, as may aspirin therapy to improve blood flow. If IUGR is threatening the well being of the fetus, early delivery may be necessary ie. via C-section. Yasmin and Adeghe (26) report a case of early-onset symmetrical fetal growth restriction in a patient with treated AS. At 20 weeks the fetal measurements corresponded with 18 weeks. A detailed scan at 29 weeks revealed measurements under the 3rd centile with oligohydroamnios and uterine artery flow suggested poor placental perfusion. The baby was delivered via C-section at 29 weeks. The placenta was calcified and partially adherent to the uterine wall. Interestingly, there are no other published studies mentioning IUGR as a complication of AS, although one would not expect it to be a rare consequence. It is possible that some cases of IUGR in women with a history of AS have been attributed to other causes, as there are potentially many confounding risk factors.
Premature Birth
Premature or preterm birth is defined as spontaneous labour followed by birth before 37 weeks of gestation. The duration of most pregnancies is around 40 weeks, with babies born between 37 and 42 weeks considered full term. There are several factors which are linked to prematurity which makes it difficult to always know the exact cause. Certain life style factors (smoking, drinking/drugs, stress etc.), and medical conditions (diabetes, hypertension, infections, underweight or obesity etc.) are associated with prematurity. Certain women are also predisposed to premature delivery: those with twin/triplet ie. multiple pregnancies, women with previous premature birth, and women with uterine or cervical abnormalities (congenital or acquired). The overall rate of premature birth in the US is 12.8% (27). However, in women with a past history of AS rates of premature delivery from 17.912-50% have been reported (9, 10, 28, 29, 30) In some cases, but not all, prematurity occurred in conjunction with abnormal placentation (eg. adherant placenta, placenta accrete and/or previa etc). Other studies have linked prematurity to induced surgical (ie. D&C) abortion but not to medical abortion, which supports a correlation between endometrial trauma and premature delivery. Note that most terminations are now carried out medically (however, unfortunately, standard management of missed or incomplete miscarriage continues to be D&C in many countries, more for cultural reasons rather than medical ones).
Premature birth is the leading cause of neonatal mortality and morbidity. Infants born prematurely are at an increased risk for both short and long-term health complications. The earlier the birth, the higher the risk for health complications. Complications are more likely to occur and with more severity in infants born before 32 weeks than after. As medical care continues to improve, infants are surviving at earlier gestational ages, however the current limit for viability is generally around 24 weeks. Potential health complications of ‘premies’ include:
-neurological problems (eg. cerebral palsy, apnea of prematurity, retinopathy of prematurity),
-respiratory problems (eg. respiratory distress syndrome),
-cardiovascular problems (eg. patent ductus arteriosus),
-gastrointestinal/metabolic disorders (eg. rickets, inguinal hernia),
-hematological conditions (eg. jaundice, anemia) and
-infections (eg. sepsis, UTI).
Pregnancy loss due to cervical insufficiency (CI), which occurs without labour and has a different etiology, is not considered premature birth. However, cervical cerclage and progesterone supplementation may be used to prevent/manage both conditions. Progesterone derivatives have been shown to reduce the frequency of premature delivery both in women with previous premature delivery (31) and women with short cervix (25).
Uterine rupture
The most common factor predisposing to uterine rupture is a uterine scar. This may be caused by D&C, C-section or hysteroscopic surgery (eg. myomectomy, reparation of congenital uterine malformations etc.). Not surprisingly, there have been several reports of uterine rupture among women with a past history of AS (7, 32, 33, 34, 35). In most of these cases, prior uterine perforation occurred during hysteroscopic adhesiolysis , however in rupture has also been reported in women without prior perforation (33). The thinning, weakened and increased fibrosis of the myometrium undoubtedly predispose to rupture of the uterus (2, 36).
This long list of potentially serious complications supports the recommendation that women who have had AS, even after correction, should be carefully monitored by a high risk Obstetrician, and preferably one who is aware of the reported complications in order to optimize the well-being of the pregnancy and the patient. These serious complications also add to a growing list of reasons why prevention of AS from occurring is more compelling than relying solely on treatment of the condition. In all of these complications endometrial damage is the common denominator which has the potential to affect placental attachment, uterine/cervical strength and/or placental perfusion. Finally, it is interesting to note that while complications and sequelae readily attributed to C-sections are being closely monitored and the number of C-sections is being audited by hospitals and organizations such as the WHO with a view to reducing their frequency (37), the same is not being done for D&C. Why not? A reduction in D&C rates would lead to fewer obstetric complications necessitating C-sections. Furthermore, the public health costs of diagnosis, surgical correction, treatment for infertility and obstetric complications resulting from D&C should be reason enough to reduce the reliance on this procedure-not to mention the impact on women's health and well-being.
REFERENCES
(numbering continued from Part I)
2.Yu, D, Wong, YM, Cheong, Y, Xia, E, and Li, TC. Asherman syndrome--one
century later. Fertil Steril 2008;89(4):759-79. Abstract
9. Capella-Allouc S, Morsad F, Rongieres-Bertrand C, et al. (1999). "Hysteroscopic treatment of severe Asherman's syndrome and subsequent fertility". Hum Reprod 14 (5): 1230–1233. Abstract11. Fernandez H, Al Najjar F, Chauvenaud-Lambling et al. (2006). "Fertility after treatment of Asherman's syndrome stage 3 and 4". J Minim Invasive Gynecol 13 (5): 398–402. Link to complete article
25. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the Risk of Preterm Birth Among Women with a Short Cervix. New England Journal of Medicine, 2007;375:(5)2, 2007; 462-469. Link to pdf
26. Yasmin H, Adeghe JH. Severe early-onset intrauterine growth restriction (IUGR) in a woman with Asherman's syndrome. J Obstet Gynaecol. 2004 ;24(3):312-4. Abstract
27. Martin, J.A., et al. Births: Final Data for 2006. National Vital Statistics Reports, volume 57, number 7, January 7, 2008.
28. Yu D, Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman’s syndrome. Fertil Steril 2007; 89(3):715-22. Abstract.
29. P.McComb, B.Wagner. Simplified therapy for Asherman"s syndrome. Fertility and Sterility; 68(6):1047-1050. Abstract
30. Protopapas A, Shushan A, Magos A. Myometrial scoring: a new technique for the management of severe Asherman's syndrome. 1998;69(5):860-4.Abstract
31. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate. New England Journal of Medicine, 2003;348(24):2379-85. Link to pdf
32. Deaton JL, Maier D, Andreoli J Jr. Spontaneous uterine rupture during pregnancy after treatment of Asherman's syndrome. Am J Obstet Gynecol. 1989;160(5 Pt 1):1053-4. Abstract
33. Shiau CS, Hsieh CC, Chiang CH, Hsieh TT, Chang MY, Chang Gung. Intrapartum spontaneous uterine rupture following uncomplicated resectoscopic treatment of Asherman's syndrome. Med J. 2005 Feb;28(2):123-7. Abstract with link to free article
34. Gürgan T, Yarali H, Urman B, Dagli V, Dogan L. Uterine rupture following hysteroscopic lysis of synechiae due to tuberculosis and uterine perforation. Hum Reprod. 1996;11(2):291-3. Abstract35. Hulka JF.Uterine rupture after treatment of Asherman's syndrome. Am J Obstet Gynecol. 1990 May;162(5):1352-3.
36. Felmus LB, Pedowitz P, Nassberg S. Spontaneous rupture of the apparently normal uterus during pregnancy. A review. Obstet Gynecol Surv 1953;8(2):155-172.
37. Nils Chaillet, Eric Dubé, Marylène Dugas, Diane Francoeur, Johanne Dubé, Sonia Gagnon, Lucie Poitras, Alexandre Dumont. Identifying barriers and facilitators towards implementing guidelines to reduce caesarean section rates in Quebec. Bulletin of the World Health Organisation 2007;85(10):733-820. Complete article
Wednesday, March 31, 2010
Complications in post AS Pregnancies (Part I)
Over the decades it has become apparent that women with a past history of Asherman’s syndrome (AS) are at an increased risk for serious obstetric complications in pregnancies that occur after successful treatment. While it was already known that those who were able to conceive without surgical correction had complicated pregnancies, it has also emerged that even after treatment, patients ran a higher risk for certain obstetric complications. Presumably this is due to the fact that even if intrauterine adhesions have been removed, acquired defects in endometrial function may persist. For example, the most severe form of Asherman’s syndrome is known as ‘unstuck’ Asherman’s syndrome where there are no intrauterine adhesions, but instead the endometrium is completely replaced by scar (connective) tissue (fibrosed, or sclerotic). Varying degrees of fibrosis may be still present in the ‘corrected’ uterus, especially if adhesions were dense and fibrous with no visible endometrium covering them on hysteroscopic view. Hormone therapy attempts to restore endometrial growth and function, however damage may be too extensive in some areas.
Although there have been numerous studies on pregnancy complications following treatment, many Obstetricians are not well informed about either the nature of these risks or of their prevalence. Awareness of these risks would allow doctors and their teams to be prepared for emergency situations which may arise and better manage the complications, safe-guarding the lives and health of both patients and their offspring.
It should be emphasized that of critical importance is that the uterine cavity is clear of adhesions (or that adhesions are minimal (ie. less than around 10% of the uterine cavity and filmy) before a patient is given the all clear to try to conceive. Thus, corrective surgery and hormonal treatment should be followed up with either HSG, SHG, or in-office/diagnostic hysteroscopy. Adhesions, especially severe ones, are known to recur and in this case further surgery is often required. Also, adhesions are preferably dissected using a mechanical method such as microscissors instead of methods which utilize thermal energy (monpolar knife, Nd:YAG laser) as the latter can necrose endometrial tissue (1) and are used in endometrial ablation procedures to treat women with excessive uterine bleeding. However, there is still the potential for complications because an adhesion-free uterus does not equate with a perfectly functioning endometrium (presumably the same reasoning applies to the correlation between AS severity and live birth outcomes). It may be thinner, irregular in thickness and/or there may be regions of fibrosis where blood flow is less than optimal and the endometrium is unresponsive to hormones.
The reported obstetric complications in women with corrected AS include:
-Miscarriage (?)
-Abnormal placentation such as:
placenta accreta
placenta increta
placenta percreta
placenta previa
uterine sacculation
-Cervical incompetency
-IUGR (intrauterine growth retardation)
-Premature birth
-Uterine rupture
Note: There is some evidence that preeclampsia may also be another complication after AS.
Miscarriages
Although to date there is not any clear indication of an increased incidence of miscarriage among women with corrected AS, it is not difficult to imagine that the same underlying causes of obstetric complications often encountered in second or third trimester could give rise to miscarriages when encountered at an earlier stage of pregnancy. For example, poor placental perfusion is an underlying cause of IUGR. However, if the embryo by chance implanted in an area where there was fibrosis or where the endometrium was particularly thin, this could also have an effect on blood flow to the area surrounding the gestational sac, leading to a first trimester miscarriage. (Those interested in the link between miscarriage and uterine blood flow should refer to: Burton and Jauniaux Placental oxidative stress: from miscarriage to preeclampsia. J Soc Gynecol Investig 2004,11:342-52.) In a review of published obstetric outcomes, Yu et al (2) observe that the rate of miscarriages in women post AS (20%) does not differ from those of the general population (20-25%). However, the rate of 20-25% represents an average of women of all ages (the rate is 14% in women under 35 and 40% among women over 40 (3)) while most of the pregnancies reported in the literature among AS patients appear to have occurred in women under 35. Thus it is possible that the miscarriage rate is actually higher if compared to the expected rate for their corresponding age group.
Abormal Placentation
Abnormal placentation is when the placenta has either implanted too low in the uterus (placenta previa) or has attached too deeply and is described as ‘morbidly adherent’. Placenta accreta and its more severe variants, placenta increta and placenta percreta, occur when the placenta has implanted too deeply, causing problems with placental detachment at delivery. These conditions arise when there is a defect in the decidua basalis allowing the anchoring villi to adhere in varying depths in the uterine wall or even beyond. Placenta increta is characterized by a total or partial absence of the decidua basalis and imperfect development of the fibrinoid layer. The myometrium is penetrated in varying depths in placenta increta. Placenta percreta is the most severe of these conditions where the placenta invades the entire myometrium sometimes even extending into the adjacent bladder or bowels. There are case reports and studies providing evidence on the correlation between placenta accreta (4,5,6,7,8,9,10,11,12), increta (7, 13) and previa (6,7) and a history of AS.
The incidence of these abnormalities is very low in the general population, 1 in 2500-7000, however among women with a history of AS it has been reported to affect 5%-31% of pregnancies (6,7, 8,9,11), a significant increase. As the basal endometrium has been damaged in women who have had Asherman’s syndrome (or a history of curettage) it is not surprising that this complication has been reported. What is surprising is that there are still many Obstetricians who are unaware of the association between Asherman’s syndrome (or D&C) and abnormally invasive placenta. Cesarean section is thought to be the most common cause of placenta accreta, however whether studies on the correlation took other factors such as prior intrauterine surgeries (D&C being the next most common gynecological surgery, but also hysteroscopic removal of myomas etc) into consideration is unclear. Another risk factor for accreta is suberosal uterine myomas (placental invasion into retroplacental or intraplacental fibroids can occur) (12). Another risk is smoking, while indirect risk factors include maternal age older than 35 years and elevated alpha-fetoprotein levels (12).
Often, it is difficult to predict abnormally invasive placenta in a pregnancy from diagnostic tools and the discovery is made at delivery. Thus ObGyns must be aware of a history of scarring in the uterus, not just from C-section but also from D&C, and be prepared for such serious complications to avoid maternal and infant morbidity and mortality. Sonography remains the primary diagnostic tool for detecting abnormally invasive placenta, however there are reports that MRI is superior, provided skilled interpretation is available.
The consequence of these complications during delivery is serious, with massive hemorrhage a major complication. Placenta accreta accounts for 7% of maternal mortality while morbidity includes massive transfusions, uroglogic injury, and fistula formation (12). Hysterectomy is the usual treatment of choice, however other options include uterine artery embolization (UAE)* and conservative management once the patient’s bleeding has been stabilized (14). The latter option allows fertility to be preserved by avoiding hysterectomy and preventing potential AS from a D&C. Note that D&C is sometimes performed in case of retained placenta, however this may lead to (or exacerbate AS) as has been reported to occur in 25% of women up to 4 weeks after delivery (15). In conservative management, prophylactic antibiotics are administered with ultrasound supervision. If the retained tissue is not expelled naturally after a period of time, it can be removed hysteroscopically (16).
Invasive placentation may also complicate first or second trimester pregnancy loss, causing heavy post D&C hemorrhage (17, 18, 19). It therefore appears that once the endometrium is damaged, a vicious cycle of complications can ensue. It would be interesting to conduct a comparative study on the incidence of RPOC in women with and without prior D&C/intrauterine surgery.
Unfortunately there is no way to prevent abnormal placentation in women with past AS. Prevention of AS through the use of drugs or hysteroscopy for RPOC following incomplete/missed miscarriage (2,20, 21) or delivery (16, 22) instead of blind D&C may prevent or at least reduce the severity of abnormal placentation. In a review of placenta accreta of Fox (23) from 1945-1969, 30.2% of all cases occurred in women who previously underwent uterine curettage. Although this review was carried out when C-sections were infrequent, D&C continues to be one of the most commonly performed procedures and it is not improbable that some cases of accreta which are attributed to C-section may actually have been caused by a prior D&C undergone by the patient.
*Note: uterine artery embolization may permanently reduce blood flow to uterus and lead to infertility and/or other complications.
Placenta previa
In most healthy pregnancies, the placenta attaches in the upper segment of the uterus (either at the posterior, anterior, or lateral walls of the uterus), also known as the fundus. Placenta previa is when the placenta attaches too low in the cervix, partially or completely covering the cervix. Most cases correct themselves as the uterus grows, however in about 0.5% of pregnancies, previa persists. It can occur alone or in combination with placenta accreta, increta or percreta. It may happen because other parts of the endometrium are damaged and unfit for implantation, or conversely because the endometrium in that area is thinner and it is therefore easier for the embryo to implant. Although C-section is a widely known cause, there is less emphasis and awareness about scarring from D&C as an important underlying cause. Placenta previa can be diagnosed via ultrasound, usually becoming apparent some time after 20 weeks of gestation (ie. at the time of the anatomy scan). Painless bleeding after 20 weeks is a symptom. As the placenta is partially or totally covering the cervix, this impedes vaginal delivery and C-section must be carried out instead. Around 1 in 200 pregnancies are affected, and presumably this incidence is higher in women with past AS. As with invasive placenta, previa can lead to hemorrhage at delivery, premature labour or delivery, and maternal or infant death. Once again, prevention is not possible in those with scarred/damaged uteri, however prevention of intrauterine scarring through reduction or replacement of D&C is a possibility.
Uterine sacculation
A sacculation or diverticulum of the pregnant uterus is a sac that is contiguous with the myometrium and opening into the uterine cavity and bearing no anatomic relationship to the cornual structures. There is at least one report of uterine sacculation occurring in a study of patients treated for AS (7). The sacculation occurred in a patient who developed minimal adhesions after an intrauterine device perforated the uterus and was removed laparascopically. It is thought to result from trauma to the myometrium secondary to injury, usually from curettage (24). Uterine sacculation predisposes to fetal malpresentation, increased fetal morbidity and mortality, abnormal placentation, uterine rupture, and postpartum hemorrhage.
Part II: Cervical incompetence, IUGR, premature birth, uterine rupture
See Part IIFor information on pregnancies where adhesions (synechiae) are present, please also see:
Effect of Asherman's syndrome on infant health.
10. Zikopoulos, KA, Kolibianakis, EM, Platteau, P, de Munck, L, Tournaye, H,
Devroey, P et al. Live delivery rates in subfertile women with Asherman's
syndrome after hysteroscopic adhesiolysis using the resectoscope or the Versapoint
system. Reprod Biomed Online 2004;8(6):720-5. Abstract
11. Fernandez H, Al Najjar F, Chauvenaud-Lambling et al. (2006). "Fertility after treatment of Asherman's syndrome stage 3 and 4". J Minim Invasive Gynecol 13 (5): 398–402.. doi:10.1016/j.jmig.2006.04.013. Link to complete article.
12. Placenta accreta: An association with fibroids and Asherman syndrome. Al-Serehi A, Mhoyan A, Brown M, Benirschke K, Hull A, Pretorius D. J Ultrasound Med 2008;27:1623-28. Abstract
13. Feng ZC, Huang YL, Sun JF, Yang BY, Xue BR, Zhuang LQ. Diagnostic and therapeutic hysteroscopy for traumatic intrauterine adhesion. Clinical analysis of 70 patients. Chin Med J (Engl). 1989 Jul;102(7):553-8. Abstract
14.Kayem G, Davy C, Goffinet F, Thomas C, Clément D, Cabrol D. Conservative versus extirpative management in cases of placenta accreta. Obstet Gynecol. 2004 Sep;104(3):531-6. Abstract
15.Eriksen, J and Kaestel, C. The incidence of uterine atresia after post-partum
curettage. A follow-up examination of 141 patients. Dan Med Bull 1960;7:50-1. Abstract
16. Goldenberg M, Schiff E, Achiron R, Lipitz S, Mashiach S. Managing residual trophoblastic tissue; Hysteroscopy for directing curettage. J Reprod Med. 1997;42(1):26-8. Abstract
17. Liu X, Fan G, Jin Z, Yang N, Jiang Y, Gai M, Guo L, Wang Y, Lang J. Lower uterine segment pregnancy with placenta increta complicating first trimester induced abortion: diagnosis and conservative management. Chin Med J. 2003;116:695–698. Abstract
18. Ecker JL, Sorem KA, Soodak L, Roberts DJ, Safon LE, Osathanondh R. Placenta increta complicating a first-trimester abortion. A case report. J Reprod Med. 1992;37:893–895. Abstract
19. Harden MA, Walters MD, Valente PT. Postabortal hemorrhage due to placenta increta: a case report. Obstet Gynecol. 1990;75:523–526. Abstract
20. Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. (2002). "Intrauterine adhesions after conservative and surgical management of spontaneous abortion". J Am Assoc Gynecol Laparosc. 9 (2): 182–185. doi:10.1016/S1074-3804(05)60129-6. Abstract
21. Friedler S, Margalioth EJ, Kafka I, Yaffe H. (1993). "Incidence of postabortion intra-uterine adhesions evaluated by hysteroscopy: a prospective study". Hum Reprod 8 (3): 442–444. Abstract
22. Li, YT, Yin, CS, and Chen, FM. Rectal administration of misoprostol for the
management of retained placenta--a preliminary report. Zhonghua Yi Xue Za Zhi
(Taipei) 2001;64(12):721-4. Abstract
23. Fox, H. Placenta accreta, 1945-1969. Obstet Gynecol Surv. 1972; 27:475-90. Link to a related article
24. Hess OW. Diverticulum of the pregnant uterus. Am J Obstet Gynecol 1950;59:391-7.
Tuesday, December 15, 2009
Miscarriage management after Asherman’s syndrome
Unfortunately, I can now talk from experience about how miscarriages can be dealt with post Asherman’s syndrome (AS), and what to expect. I lost my pregnancy at 14 weeks due to a trisomy 21 detected by karyotype analysis and QF-PCR of chorionic villi sampling. The first inkling that something was wrong was at the 12 week scan. Actually, the blood serum levels of PAPP-A and bHCG I’d had during the 11th week already showed a problem, but it wasn’t until my ultrasound that I learned of this. The ultrasound only confirmed that things were not right. Only two weeks earlier I’d had another ultrasound and all seemed fine- the heart beat, the CRL, etc. Now the nuchal fold measured 7mm and there was hydrops- an accumulation of fluid around the fetus. I was told there was a high probability that the pregnancy would end spontaneously.
Fast forward to week 14 and there was no longer a heartbeat.
I’d always talked about misoprostol and ironically now I would have to use it myself. There was no way on earth I’d undergo another D&C (suction curettage or whatever you want to called this blind invasive procedure)- the procedure which caused Asherman’s syndrome when I had it 3 years earlier for a blighted ovum. I could not risk exacerbating the condition. If only my initial ObGyn had agreed to treat me with misoprostol I could have avoided all the surgery and heart ache that followed. I’m quite sure I’d have a child by now.
Since I was relatively far into the pregnancy and the fetus had developed to 14 weeks before dying spontaneously, I booked in the hospital for the misoprostol induction. I don’t know which hospitals/ObGyns use misoprostol regularly, however, in the interest of informing women, my procedure was performed at the Royal Hospital for Women in Randwick (Sydney). I’m sure there are other hospitals (and doctors) that are familiar with misoprostol use, and yes, it is completely legal even if it has not been approved by the TGA (Australia's equivalent of the FDA) for gynecological indications for dubious reasons. By the way, the doctor who refused to give me misoprostol works at St George Hospital. I’d be interested to know if that hospital carries out medical management of miscarriage- please drop me a line or comment below if you know.
In total, I was given a dose of 1 mg (milligram) of misoprostol over the course of a day. Initially, one pill ie. 200 mcg (vaginal) was given to test for any adverse reactions, allergies etc. I began cramping but there was no bleeding. About 5 hours later cervical dilation was checked (closed) and I was given 400 mcg (2 pills). The cramping intensified, but again, there was no bleeding. Shortly after my third and final dose, about 5 hours after the last dose, I began having strong contractions. It was quite painful so I’d definitely recommend panadeine forte. Strangely, there was still no bleeding unlike with my first miscarriage which began like a period. About 40 minutes after my final dose, the waters broke and amniotic fluid spilled out soaking the bed. After this point the pain stopped although I was still feeling crampy for at least a week afterwards. Roughly half an hour after the waters broke, I delivered the tiny baby. The umbilical cord was thin and weak and broke off from the placenta. It is at this point that I began bleeding. I continued bleeding heavily throughout the night and the next day. I also bled strongly for about a week afterwards and on and off during the following week. The placenta should have come out soon afterwards but it was not until 3.5 hours passed that it did. Luckily I’d discussed the possibility of retained placenta previously with my ObGyn and we agreed to wait it out (normally most doctors would jump at the opportunity to do a D&C in this situation) while the nurses and midwives monitored me closely for signs of infection and hemorrhage. As it’s difficult to know if the placenta is complete on visual inspection, and women with a history of Asherman’s syndrome- even after surgical correction- are at an increased risk of placental conditions such as placenta accreta, percreta, increta, and previa, I knew retained placenta was a possibility.
Before the placenta delivered my temperature reached 40 C and the midwife was somewhat concerned, however misoprostol itself can cause fever. The morning after, my blood pressure was 90 on 60 (normally it is around 110-115/65-70) and I was told this could be due to blood loss.
The next morning I underwent an ultrasound to check for retained placental fragments. Around 32 mls of material was found in the uterus but it was impossible to tell whether this was simply blood and blood clots, or if there were retained products of conception (RPOC). Doppler flow analysis suggested that there were retained placental fragments in the posterior of the uterus- the same area where the placenta had implanted in this pregnancy. I had another ultrasound a week after the first. The second ultrasound showed that the fluid in the uterus had roughly halved, but it was still not possible to tell for sure via ultrasound whether there were retained products.
In the following week I bled little despite having around 18 mls of content in my uterus so I became concerned that perhaps there were retained fragments. This would not be a surprise given my pregnancy reached second trimester and my previous history of Asherman’s syndrome. I contacted my trusted Asherman’s syndrome specialist for a hysteroscopic procedure to remove any retained fragments of placenta. This procedure was done 3 weeks after the misoprostol treatment. It turns out I did have many retained fragments which were gently scraped off using the hysteroscope itself. Luckily I did not have any clinical infection from the retained tissue (perhaps just 'subclinical' ;) ?). There were no adhesions. I was given prophylactic antibiotics to prevent infection after the surgery.
I should also mention that to prevent any possible adhesions, I was prescribed 2mg/day progynova (a synthetic estrogen) for 28 days by an Asherman’s syndrome specialist. The other option was Premarin (0.625 mg). These help the endometrium grow and thereby prevent uterine walls from adhering in the case of scarring.
I’m now awaiting my next period after which I’ll have a mid cycle scan to measure endometrial thickness at ovulation, and either an in--office hysteroscopy or an HSG to check for adhesions. Hopefully the removal of RPOCs did not cause any scarring.
Note that the dose of misoprostol I was given was decided according to my pregnancy stage (14 weeks) and status (fetal demise). Doses vary and guidelines should be adhered to.
Here is a summary of my suggestions (as a non MD) if you find yourself in this situation:
1. Don’t have a D&C for a miscarriage as it can cause further damage especially if you have had AS previously. Also, your endometrium may get thinner each time you have a D&C.
2. Misoprostol helps clear out most of the uterine contents. It is more painful than a D&C but worth it in the long run- unless you are not interested in preserving your fertility. NOTE: If you have had a previous Cesarean section or uterine perforation or severe AS, discuss with your ObGyn to see if misoprostol is safe for you (or you may need to take a lower dose than what I was given).
3. You should have estrogen therapy to prevent adhesions from forming. I'm not sure if this is 100% necessary but Asherman's specialists recommend it. Some women didn't use it because of adverse reactions to estrogen (blood clots etc.) and they did not develop adhesions.
4. You will probably have retained tissue and require a hysteroscopy (not a blind D&C!!) to remove it. In most cases if you have had a missed miscarriage you will need to either use misoprostol or, alternatively, wait to miscarry before hysteroscopy can be effective, otherwise there is just too much tissue and blood to work with.
5. Have a mid cycle scan to measure endometrial thickness after your first post-treatment period and always check that your uterine cavity is free of adhesions before you attempt to conceive again just in case. An in-office hysteroscopy is best but failing that, an HSG can be done.
There are also some implications that can be speculated:
1. It may take a few hours for the placenta to deliver when using misoprostol post AS if you are beyond the first trimester.
2. It is likely that if you have had AS, you will have retained products after every future miscarriage. Hysteroscopic removal of tissue allows the doctor to view your uterus as he/she clears it. Note: Hysteroscopy itself can cause complications if undertaken by an unexperienced or unskilled doctor. Please see only a highly experienced specialist.
3. You should anticipate that you may have placenta accreta in a future pregnancy particularly if the placenta does not deliver when expected or you have had confirmed RPOC. Obviously, any woman with past AS should be monitored throughout their pregnancy by a high-risk Obstetrician.
I will try to write about the known pregnancy complications in women with a history of AS in the near future.
There are two more interesting points: Initially I believed that I may not get RPOC because the placenta had implanted in a region which was never affected by intrauterine adhesions. The fact that it is possible to get RPOC in a new, previously unaffected area suggests that perhaps the placenta implants deeply because the endometrium is slightly thinner than it should be ideally. Or maybe blood flow to the uterus is somehow affected and in order for the pregnancy to establish the placenta needs to invade the endometrium more deeply.
Secondly, I have to question once again whether there is any truth at all to the unfounded claim by certain doctors that Asherman’s syndrome can occur ‘spontaneously’ after miscarriage. I would have to have actual evidence to believe this. In my own case I had no adhesions 2 weeks after miscarrying using misoprostol-and this is even after having had intrauterine adhesions in the past (from a D&C). In other words they did not reoccur, nor did any new ones develop. I suspect that if I was treated with blind D&C rather than misoprostol, lo and behold I would develop ‘spontaneous’ adhesions in a new region: the posterior region of my uterus (where the RPOC were). It doesn't make sense for such an evolutionarily destructive mechanism to occur in nature (unless extremely rarely).
In retrospect, I have to wonder why my first Obgyn (ie the one who caused me to have AS) so steadfastly rejected my request to use misoprostol instead of a D&C when it can be used even until the third trimester. He made me believe that it could only be used until 8 or 10 weeks. I also wonder why, as a doctor who was aware about Asherman’s syndrome, my strong concern about acquiring it, and knew of the Asherman’s syndrome support group, he did not refer me for a hysteroscopic removal the supposed RPOC I had? What, may I ask, is the purpose of informing gynecologists about Asherman’s syndrome if they will continue to perform damaging D&Cs while refusing to offer other options? ‘Consent’ for D&Cs is hardly possible when other options are not made available. Please, let us not make Obstetricians/gynecolgists believe that treatment is so simple and effective that causing Asherman’s syndrome is just a little glitch with few consequences for the patient.
Finally, my experience has shown once again that prevention of Asherman’s syndrome is best: the condition leads to a cycle of costly and lengthy complications with retained products (not to mention possible obstetric complications in future pregnancies) which could be avoided if medical management (ie. misoprostol) was used in the first instance.
Fast forward to week 14 and there was no longer a heartbeat.
I’d always talked about misoprostol and ironically now I would have to use it myself. There was no way on earth I’d undergo another D&C (suction curettage or whatever you want to called this blind invasive procedure)- the procedure which caused Asherman’s syndrome when I had it 3 years earlier for a blighted ovum. I could not risk exacerbating the condition. If only my initial ObGyn had agreed to treat me with misoprostol I could have avoided all the surgery and heart ache that followed. I’m quite sure I’d have a child by now.
Since I was relatively far into the pregnancy and the fetus had developed to 14 weeks before dying spontaneously, I booked in the hospital for the misoprostol induction. I don’t know which hospitals/ObGyns use misoprostol regularly, however, in the interest of informing women, my procedure was performed at the Royal Hospital for Women in Randwick (Sydney). I’m sure there are other hospitals (and doctors) that are familiar with misoprostol use, and yes, it is completely legal even if it has not been approved by the TGA (Australia's equivalent of the FDA) for gynecological indications for dubious reasons. By the way, the doctor who refused to give me misoprostol works at St George Hospital. I’d be interested to know if that hospital carries out medical management of miscarriage- please drop me a line or comment below if you know.
In total, I was given a dose of 1 mg (milligram) of misoprostol over the course of a day. Initially, one pill ie. 200 mcg (vaginal) was given to test for any adverse reactions, allergies etc. I began cramping but there was no bleeding. About 5 hours later cervical dilation was checked (closed) and I was given 400 mcg (2 pills). The cramping intensified, but again, there was no bleeding. Shortly after my third and final dose, about 5 hours after the last dose, I began having strong contractions. It was quite painful so I’d definitely recommend panadeine forte. Strangely, there was still no bleeding unlike with my first miscarriage which began like a period. About 40 minutes after my final dose, the waters broke and amniotic fluid spilled out soaking the bed. After this point the pain stopped although I was still feeling crampy for at least a week afterwards. Roughly half an hour after the waters broke, I delivered the tiny baby. The umbilical cord was thin and weak and broke off from the placenta. It is at this point that I began bleeding. I continued bleeding heavily throughout the night and the next day. I also bled strongly for about a week afterwards and on and off during the following week. The placenta should have come out soon afterwards but it was not until 3.5 hours passed that it did. Luckily I’d discussed the possibility of retained placenta previously with my ObGyn and we agreed to wait it out (normally most doctors would jump at the opportunity to do a D&C in this situation) while the nurses and midwives monitored me closely for signs of infection and hemorrhage. As it’s difficult to know if the placenta is complete on visual inspection, and women with a history of Asherman’s syndrome- even after surgical correction- are at an increased risk of placental conditions such as placenta accreta, percreta, increta, and previa, I knew retained placenta was a possibility.
Before the placenta delivered my temperature reached 40 C and the midwife was somewhat concerned, however misoprostol itself can cause fever. The morning after, my blood pressure was 90 on 60 (normally it is around 110-115/65-70) and I was told this could be due to blood loss.
The next morning I underwent an ultrasound to check for retained placental fragments. Around 32 mls of material was found in the uterus but it was impossible to tell whether this was simply blood and blood clots, or if there were retained products of conception (RPOC). Doppler flow analysis suggested that there were retained placental fragments in the posterior of the uterus- the same area where the placenta had implanted in this pregnancy. I had another ultrasound a week after the first. The second ultrasound showed that the fluid in the uterus had roughly halved, but it was still not possible to tell for sure via ultrasound whether there were retained products.
In the following week I bled little despite having around 18 mls of content in my uterus so I became concerned that perhaps there were retained fragments. This would not be a surprise given my pregnancy reached second trimester and my previous history of Asherman’s syndrome. I contacted my trusted Asherman’s syndrome specialist for a hysteroscopic procedure to remove any retained fragments of placenta. This procedure was done 3 weeks after the misoprostol treatment. It turns out I did have many retained fragments which were gently scraped off using the hysteroscope itself. Luckily I did not have any clinical infection from the retained tissue (perhaps just 'subclinical' ;) ?). There were no adhesions. I was given prophylactic antibiotics to prevent infection after the surgery.
I should also mention that to prevent any possible adhesions, I was prescribed 2mg/day progynova (a synthetic estrogen) for 28 days by an Asherman’s syndrome specialist. The other option was Premarin (0.625 mg). These help the endometrium grow and thereby prevent uterine walls from adhering in the case of scarring.
I’m now awaiting my next period after which I’ll have a mid cycle scan to measure endometrial thickness at ovulation, and either an in--office hysteroscopy or an HSG to check for adhesions. Hopefully the removal of RPOCs did not cause any scarring.
Note that the dose of misoprostol I was given was decided according to my pregnancy stage (14 weeks) and status (fetal demise). Doses vary and guidelines should be adhered to.
Here is a summary of my suggestions (as a non MD) if you find yourself in this situation:
1. Don’t have a D&C for a miscarriage as it can cause further damage especially if you have had AS previously. Also, your endometrium may get thinner each time you have a D&C.
2. Misoprostol helps clear out most of the uterine contents. It is more painful than a D&C but worth it in the long run- unless you are not interested in preserving your fertility. NOTE: If you have had a previous Cesarean section or uterine perforation or severe AS, discuss with your ObGyn to see if misoprostol is safe for you (or you may need to take a lower dose than what I was given).
3. You should have estrogen therapy to prevent adhesions from forming. I'm not sure if this is 100% necessary but Asherman's specialists recommend it. Some women didn't use it because of adverse reactions to estrogen (blood clots etc.) and they did not develop adhesions.
4. You will probably have retained tissue and require a hysteroscopy (not a blind D&C!!) to remove it. In most cases if you have had a missed miscarriage you will need to either use misoprostol or, alternatively, wait to miscarry before hysteroscopy can be effective, otherwise there is just too much tissue and blood to work with.
5. Have a mid cycle scan to measure endometrial thickness after your first post-treatment period and always check that your uterine cavity is free of adhesions before you attempt to conceive again just in case. An in-office hysteroscopy is best but failing that, an HSG can be done.
There are also some implications that can be speculated:
1. It may take a few hours for the placenta to deliver when using misoprostol post AS if you are beyond the first trimester.
2. It is likely that if you have had AS, you will have retained products after every future miscarriage. Hysteroscopic removal of tissue allows the doctor to view your uterus as he/she clears it. Note: Hysteroscopy itself can cause complications if undertaken by an unexperienced or unskilled doctor. Please see only a highly experienced specialist.
3. You should anticipate that you may have placenta accreta in a future pregnancy particularly if the placenta does not deliver when expected or you have had confirmed RPOC. Obviously, any woman with past AS should be monitored throughout their pregnancy by a high-risk Obstetrician.
I will try to write about the known pregnancy complications in women with a history of AS in the near future.
There are two more interesting points: Initially I believed that I may not get RPOC because the placenta had implanted in a region which was never affected by intrauterine adhesions. The fact that it is possible to get RPOC in a new, previously unaffected area suggests that perhaps the placenta implants deeply because the endometrium is slightly thinner than it should be ideally. Or maybe blood flow to the uterus is somehow affected and in order for the pregnancy to establish the placenta needs to invade the endometrium more deeply.
Secondly, I have to question once again whether there is any truth at all to the unfounded claim by certain doctors that Asherman’s syndrome can occur ‘spontaneously’ after miscarriage. I would have to have actual evidence to believe this. In my own case I had no adhesions 2 weeks after miscarrying using misoprostol-and this is even after having had intrauterine adhesions in the past (from a D&C). In other words they did not reoccur, nor did any new ones develop. I suspect that if I was treated with blind D&C rather than misoprostol, lo and behold I would develop ‘spontaneous’ adhesions in a new region: the posterior region of my uterus (where the RPOC were). It doesn't make sense for such an evolutionarily destructive mechanism to occur in nature (unless extremely rarely).
In retrospect, I have to wonder why my first Obgyn (ie the one who caused me to have AS) so steadfastly rejected my request to use misoprostol instead of a D&C when it can be used even until the third trimester. He made me believe that it could only be used until 8 or 10 weeks. I also wonder why, as a doctor who was aware about Asherman’s syndrome, my strong concern about acquiring it, and knew of the Asherman’s syndrome support group, he did not refer me for a hysteroscopic removal the supposed RPOC I had? What, may I ask, is the purpose of informing gynecologists about Asherman’s syndrome if they will continue to perform damaging D&Cs while refusing to offer other options? ‘Consent’ for D&Cs is hardly possible when other options are not made available. Please, let us not make Obstetricians/gynecolgists believe that treatment is so simple and effective that causing Asherman’s syndrome is just a little glitch with few consequences for the patient.
Finally, my experience has shown once again that prevention of Asherman’s syndrome is best: the condition leads to a cycle of costly and lengthy complications with retained products (not to mention possible obstetric complications in future pregnancies) which could be avoided if medical management (ie. misoprostol) was used in the first instance.
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