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.


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 II
For 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.