Subsequent Reproductive Outcome Research Articles

O-051 Refreezing and rebiopsy – are these worth it?

Abstract Preimplantation genetic testing of embryos offers the opportunity to avoid the transmission of hereditary disorders to the offspring by selecting out embryos affected by a single gene mutation or mutations (PGT-M), structural rearrangements of chromosomes (PGT-SR), aneuploidy (PGT-A) as well as polygenic risk (PGT-P). Over the last two decades, laboratory techniques have seen tremendous developments including extended embryo culture to blastocyst stage, trophectoderm biopsy and vitrification. The latter technique is highly efficient and allows multiple freezing and warming cycles when performed in proficient laboratories. At the same time whole genome analysis techniques provide the opportunity to analyse embryonic DNA in great detail for multiple indications simultaneously. The PGT process is sensitive to both biological and technical issues which sometimes lead to a failed PGT result. Failure of PGT diagnosis is reported to occur in between 2-12% of PGT cycles depending on the methodology used. The main causes of inconclusive diagnosis are DNA amplification failure and non-concurrent results. Independent variables that influence inconclusive results are day of embryo biopsy, number of cells taken at biopsy and the quality of the IVF laboratory. In order to seize every opportunity in reaching a diagnosis and optimize reproductive outcome for the patient, rebiopsy and retesting (double biopsy and double cryopreservation) can be performed. In situations where embryos need to be biopsied for PGT for reasons of newly found genetic indications or the clinical need for PGT-A, and after an initial cryopreservation, single biopsy and double cryopreservation may be performed with potential effect on subsequent reproductive outcome. A limited number of studies have addressed both the feasibility as well as the success rate of rebiopsy and refreezing. Most studies conclude that the technique is efficient in terms of diagnostic efficiency and reproductive outcome, when performed in expert laboratories. A few studies have addressed the health of the children after multiple biopsy and multiple freezing and have not shown increased risks. Larger studies are needed to establish the true clinical and health-economic value of rebiopsy and refreezing. The speaker will give an overview of existing evidence in literature and assess whether it is safe and worthwile to go the extra mile and consider refreezing and rebiopsy for PGT. Trial registration number XXXX

Quantifying CD138+ cells in the endometrium to assess chronic endometritis in women at risk of recurrent pregnancy loss: A prospective cohort study and rapid review.

To determine the value of uterine CD138+ cells, as a marker of chronic endometritis, in predicting subsequent reproductive outcome in women with history of recurrent pregnancy loss. A prospective longitudinal study. Tertiary specialized clinic. Women with history of recurrent pregnancy loss or implantation failure over a 12-months follow-up period. We quantified the CD138+ cells/high powered field (hpf) using immunohistochemistry and image analysis of endometrial biopsies obtained during the secretory stage post ovulation. Live birth and subsequent pregnancy loss. We calculated the receiver operator curve for predicting subsequent pregnancy loss and reported using relative risk (RR) and 95% confidence intervals (CI). We enrolled 344 women of whom 88 became pregnant (88/344, 25.5%). Half of them had a subsequent live birth (47/88, 53%) and the rest lost their pregnancy (41/88, 46%). The median CD138+ score was significantly lower in the live birth group (P < 0.005) and women with a CD138+ score ≥ 16/hpf had a higher risk of subsequent miscarriage (RR 10.0, 95% CI 2.78-36.02). CD138+ cells count showed a good prediction for subsequent pregnancy loss in high-risk women with an area under the curve of 0.75 (95% CI 0.59-0.82, P = 0.01). A cut-off value of 4-6 cells/hpf offered the best predictive accuracy with higher scores predicting worse reproductive outcome. Our findings are limited by the small event rate and the sample size of our cohort. Quantifying CD138+ cells by immunohistochemistry in women with a history of recurrent pregnancy loss is helpful to diagnose chronic endometritis and predict subsequent reproductive outcome.

Fertility preservation for patients on gonadotoxic treatment recommendations for clinical practice by Fertility Preservation Society (India)

Aim: Objective of this document is to provide guidance to health care professionals on fertility preservation (FP) for Indian patients undergoing cancer treatment. Participants: Extensive deliberations, discussion and brain storming was done with different reproductive medicine (RM) specialists, medical, radiation, surgical, gynaecological and oncologists and haematologists to develop the recommendations. Evidence: A systematic review of the literature published up to December 2020 was carried out using PubMed and Cochrane Collaboration Library. International guidelines, cohort studies, case series, observational studies and randomized controlled trials currently available in literature were reviewed. Supplemental searches were made for individual conditions like lymphoma, leukaemia, haematological conditions, breast cancer, gynaecological cancers, immune disorders. Indian data on fertility preservation was limited to case series, hence opinion of experts was taken into account for the recommendations on fertility preservation in India. Cancer incidence and survival rates were taken from the Indian cancer registry (ICR). A panel of RM specialists across India reviewed the evidence and offered recommendations for Indian patients. Process: Meetings were held with leading oncologists from major cancer institutes in India – Delhi: AIIMS, Medanta, Indraprastha Apollo hospital, Max SS hospital, Mumbai: Bombay Hospital; Miraj: Siddhivinayak hospital; Kolkata: Tata Medical Centre; Bangalore: Mazumdar Shaw Cancer Centre; Narayana Health City and HCG; The working group for the recommendation committee included members from the Fertility Preservation Society (India) and participating oncology experts. Conclusions: The Fertility Preservation Society (India) recommends that oncologists should discuss the risk of infertility resulting from cancer treatment with patients of reproductive age group, at the earliest opportunity and provide initial information regarding the availability of FP. Patients with a good oncological prognosis at risk of infertility and interested in preservation of their fertility, should be referred to a reproductive medicine expert as early as possible after confirmatory diagnosis. Details of FP procedures including risks and subsequent reproductive outcome should be explained in detail by the reproductive medicine specialist. Genetic and social counselling should be made available to the patient to aid in taking an informed decision. Limiting factors in India include lack of awareness of FP options and availability, cost, lack of insurance coverage, experimental nature of some FP procedures.

Subsequent Reproductive Outcome Among Women With Peripartum Cardiomyopathy: A Nationwide Study

(BJOG. 2018;125:1018–1025) Peripartum cardiomyopathy (PPCM) is a condition characterized by idiopathic heart failure late in pregnancy or within 6 months postpartum. It is diagnosed when no other identifiable cause of heart failture is identified and left ventricular systolic function is impaired with left ventricular ejection fraction (LVEF) of 45% of lower. Women who have developed PPCM must receive counseling on potential risks in subsequent pregnancies, but there are not clear guidelines or literature on reproductive outcomes after PPCM. Previous studies reported increased relapse rates if LVEF was still impaired. This study used a Danish cohort of women to investigate perinatal outcomes in women with prior PPCM.

Authors' reply re: Subsequent reproductive outcome among women with peripartum cardiomyopathy: a nationwide study

Authors' reply re: Subsequent reproductive outcome among women with peripartum cardiomyopathy: a nationwide study

Subsequent reproductive outcome among women with peripartum cardiomyopathy: a nationwide study.

To describe the subsequent reproductive outcome for a Danish nationwide cohort of women with peripartum cardiomyopathy (PPCM). Nationwide historic cohort study. Secondary and tertiary centres across Denmark. Women with PPCM. Sixty-one women with PPCM during 2005-2014 were identified in a nationwide, registry-based study and the diagnosis was validated through audit of patient records. A new search for subsequent reproductive outcome in this cohort from 2005-2016 was conducted in the Danish National Birth Registry and the Danish National Patient Registry. Detailed clinical data were obtained from patient records. Sterilisations and subsequent reproductive outcomes after PPCM, including all pregnancies, miscarriages, terminations and deliveries. Of 61 women with PPCM, 13 (21%) had a total of 16 subsequent pregnancies resulting in one miscarriage, seven early terminations, one ectopic pregnancy and seven liveborn children. There were no maternal deaths or significant cardiac events during pregnancy, but one woman, who gave birth to a liveborn child, had a relapse of PPCM 7 weeks postpartum. None of the six women who had a first trimester termination, experienced relapse of PPCM. Of the 13 women with a subsequent pregnancy, 62% had prior to this been advised against a new pregnancy due to the risk of recurrent PPCM. A total of four women (6.6%) were sterilised. Peripartum cardiomyopathy affects women's reproduction with few subsequent pregnancies resulting in a liveborn child. The finding of a 1/7 relapse among women with recovered LVEF is in accordance with most previous studies. Outcome in pregnancies after peripartum cardiomyopathy: results from the first nationwide study.

Optimizing dietary lipid use to improve essential fatty acid status and reproductive performance of the modern lactating sow: a review.

Dietary lipid supplementation benefits the prolific and high-producing modern lactating sow. A comprehensive review of recent studies showed that lipid supplementation increases average daily energy intake, which is partitioned for lactation as indicated by greater milk fat output and improved litter growth rate. Recent compelling findings showed that addition of particular lipids during lactation improved the subsequent reproductive outcome of sows. Such benefits were related to the level of dietary essential fatty acids (EFA, linoleic acid, C18:2n-6; and α-linolenic acid, C18:3n-3) during lactation. Lactation diets without supplemental EFA resulted in a pronounced negative balance (intake minus milk output) of linoleic (−25.49 g/d) and α-linolenic acid (−2.75 g/d); which compromised sow fertility (farrowing rate < 75 % and culling rates > 25 % of weaned sows). This phenomenon seems to be increasingly important with advancing sow age because of a progressive reduction of body EFA pool over successive lactations. The net effect of supplemental EFA during lactation was to create a positive EFA balance, which improved the subsequent reproduction of sows. Adequate linoleic acid intake improved the proportion of sows that farrowed in the subsequent cycle (Farrowing rate (%) = [(−1.5 × 10−3 × linoleic acid intake (g/d)2) + (0.53 × linoleic acid intake (g/d)) + (45.2)]; quadratic P = 0.002, R2 = 0.997, RMSE = 0.031). In addition, increasing linoleic acid intake increased the number of pigs born in the subsequent cycle (total pigs born (n) = [(9.4 × 10−5 × linoleic acid intake (g/d)2) + (0.04 × linoleic acid intake (g/d)) + (10.94)]; quadratic P = 0.002, R2 = 0.997, RMSE = 0.031). Supplemental α-linolenic acid resulted in a rapid return to estrus (sows bred: sows weaned = 94.2 %; wean-to-estrus interval = 4.0 d) and achieved a high retention of pregnancy (sows pregnant: sows bred = 98 %). Collectively, we conclude that a minimum dietary intake of 10 g/d of α-linolenic acid, simultaneous with a minimum of 125 g/d of linoleic acid should be provided to ≥ 95 % of the sows; thereby, achieving a maximum sow reproductive efficiency through multiple mechanisms that include rapid return to estrus, high maintenance of pregnancy and large subsequent litter size in mature sows, that appear to be susceptible to EFA deficiency.

Sperm Chromatin Immaturity Observed in Short Abstinence Ejaculates Affects DNA Integrity and Longevity In Vitro.

BackgroundThe influence of ejaculatory abstinence (EA) on semen parameters and subsequent reproductive outcome is still debatable; hence understanding the impact of EA on sperm structural and functional integrity may provide a valuable information on predicting successful clinical outcome.ObjectiveTo understand the influence of EA on sperm chromatin maturity, integrity, longevity and global methylation status.MethodsThis experimental prospective study included 76 ejaculates from 19 healthy volunteers who provided ejaculates after observing 1, 3, 5 and 7 days of abstinence. Sperm chromatin maturity, DNA integrity and global methylation status were assessed in the neat ejaculate. Sperm motility, DNA integrity and longevity were assessed in the processed fraction of the fresh and frozen-thawed ejaculates to determine their association with the length of EA.ResultsSpermatozoa from 1 day ejaculatory abstinence (EA-1) displayed significantly higher level of sperm chromatin immaturity in comparison to EA-3 (P < 0.05) and EA-5 (P < 0.01) whereas; the number of 5-methyl cytosine immunostained spermatozoa did not vary significantly across groups. On the other hand, in vitro incubation of processed ejaculate from EA-1 resulted in approximately 20 and 40 fold increase in the DNA fragmented spermatozoa at the end of 6 and 24h respectively (P < 0.01–0.001).ConclusionUse of short-term EA for therapeutic fertilization would be a clinically valuable strategy to improve the DNA quality. However, use of such spermatozoa after prolonged incubation in vitro should be avoided as it can carry a substantial risk of transmitting DNA fragmentation to the oocytes.

Sperm chromatin integrity may predict future fertility for unexplained recurrent spontaneous abortion patients

The pathogenesis of recurrent spontaneous abortion (RSA) is multi-factorial, complex and poorly understood. In the present study, semen parameters, including sperm chromatin integrity, sperm concentration, sperm motility and sperm morphology, were compared between 111 men whose partners had a history of unexplained RSA (RSA group) and 30 healthy fertile men (control group). The RSA group was further separated into three subgroups, depending on their reproductive outcome during the 12 months after they were enrolled in the study: the pregnancy subgroup consisted of 43 men whose partners achieved a successful pregnancy up to at least the 24th week of gestation; the abortion subgroup included 31 men whose partners experienced further abortions; and the infertile subgroup had 37 men whose partners did not have any positive pregnancy test after regular, unprotected intercourse. Significantly lower proportion of sperm with normal morphology was found in the abortion subgroup (14.7 ± 4.3%) than in the control group (17.5 ± 5.0%). Sperm concentrations were significantly lower in the infertile subgroup (55.7 ± 24.1%) than in the controls (68.6 ± 27.8%). The rates of abnormal sperm chromatin integrity were significantly higher in the abortion (16.7 ± 7.7%) and infertile (16.3 ± 6.6%) subgroups, compared to the control group (13.0 ± 4.4%). Logistic regression analysis showed that the subsequent reproductive outcome of the 111 RSA patients was negatively correlated to the rates of abnormal sperm chromatin integrity. In conclusion, sperm chromatin integrity, sperm morphology, and sperm concentration were associated with future reproductive outcome of RSA patients. The sperm chromatin integrity was a significant predictor for future abortion and infertility.

Fertilité et grossesses après prise en charge invasive des hémorragies du postpartum

Ligation of the internal iliac arteries and embolization of the uterine arteries are two techniques routinely used in the management of postpartum hemorrhage. The objective of this study was to examine the long-term consequences of these techniques on women's subsequent reproductive outcome and subsequent delivery morbidity. Retrospective study including women who underwent ligation and those who underwent embolization, for the treatment of postpartum hemorrhage. We analyzed resumption of menses, fertility, pregnancy and delivery outcome after each treatment. The study included 85women who underwent ligation and 90who had embolization to treat postpartum hemorrhage. No adverse event related to menses, fertility, or pregnancy outcome followed either treatment. However, the rate of recurrent hemorrhage was high: 26% after ligation and 39% after embolization. All recurrences were treated medically in the ligation group, but in the embolization group, 42% (five of 12patients) required invasive treatment and 33% (four patients) transfusions. From the perspective of subsequent menses, fertility and pregnancy outcome, both ligation and embolization are safe procedures for the management of postpartum hemorrhage. However, our results showed a high risk of recurrent postpartum hemorrhage after both treatments. Recurrences seemed more serious after the latter.

Clinical characteristics and outcomes of critically ill obstetric patients: a ten-year review

BACKGROUND AND OBJECTIVES:Pregnancy and delivery can involve complications that necessitate admission to critical care facilities. The objective of our study was to assess the incidence, indications, and outcomes of obstetric patients requiring admission to an intensive care unit (ICU) in a tertiary care hospital, in Saudi Arabia.DESIGN AND SETTING:Retrospective cohort study of consecutive obstetric admissions to the ICU at the King Abdulaziz Medical City over a 10-year period.PATIENTS AND METHODS:We collected baseline demographic data and acute physiology and chronic health evaluation II (APACHE II) scores. ICU mortality was the primary outcome.RESULTS:Over 10 years, 75 obstetric patients were admitted to the ICU, and 59 of these patients (78.6%) were admitted during the antepartum period. The main obstetric indication for ICU admission was pregnancy-induced hypertension (21 patients, 28%) and the leading non-obstetric indication was sepsis (12 patients, 16%). The APACHE II score was 19.59 (15.05). The predicted mortality rate based on the APACHE II score was 21.97%; however, there were only six maternal deaths (8%) among the obstetric patients admitted to the ICU.CONCLUSION:The overall mortality was low. A team approach facilitated the application of optimal care to these patients. Obstetric patients had better outcomes than those predicted by the APACHE II scores. Appropriate antenatal care is important for preventing obstetric complications.

Subsequent reproductive outcome in women who have experienced a potentially life-threatening condition or a maternal near-miss during pregnancy

OBJECTIVE:To evaluate the long-term reproductive consequences that affect women who have experienced potentially life-threatening or life-threatening (near-miss) maternal complications.INTRODUCTION:Although advances have been made in reducing maternal death, few studies have investigated the long-term repercussions of significant events such as severe maternal morbidity and maternal near-misses. These repercussions may be long-lasting and negatively affect quality of life.METHODS:A total of 382 women who had experienced a potentially life-threatening pregnancy-related condition within the last five years were analyzed in this retrospective cohort study. A control group of 188 women who gave birth without complications was also included. Trained interviewers contacted the subjects by telephone and completed a pre-coded, structured questionnaire on reproductive health. Data were analyzed using odds ratios adjusted for age. The main outcome measures were occurrence and outcome of subsequent pregnancies.RESULTS: The estimated risk of becoming infertile as a result of tubal ligation or hysterectomy was 3.5 times higher in women who experienced a maternal near-miss or severe maternal morbidity during the index pregnancy as compared to controls. Likewise, the risk of complications in subsequent pregnancies was five times greater in women who had experienced severe maternal morbidity. However, no differences were found in the occurrence or number of subsequent pregnancies or perinatal outcome.CONCLUSION: The occurrence of a life-threatening or potentially life-threatening maternal condition reduces future reproductive potential and increases the risk of complications in subsequent pregnancies.

Safety studies of sperm agglutinating factor produced by Staphylococcus aureus as a vaginal contraceptive: in vivo studies

Sperm agglutinating factor (SAF) isolated from Staphylococcus aureus when applied at concentration 10 μg before mating completely prevented conception in the mouse. The objective of the present study was to evaluate its safety, as safety is an important concern to be addressed before a compound is selected for contraceptive use. Our results showed that SAF has a very high safety profile. Vaginal application of SAF at 10 μg to the mouse for 14 consecutive days caused no systemic toxicity and vaginal irritation as indicated by lack of effect on organ weights and histology. Moreover, no adverse effect was observed on the subsequent reproductive capability, peritnatal outcome and growth and development of the offspring. SAF (10 μg) did not irritate the skin or penile mucosa. Oral administration of 2 mg/kg body weight of SAF did not show any toxicity to reproductive and non-reproductive organs. Therefore, SAF with spermicidal activity and lack of toxicity may have the potential to become the active ingredient of a vaginal contraceptive.

ORIGINAL ARTICLE: Cell‐Surface CD200 May Predict Efficacy of Paternal Mononuclear Leukocyte Immunotherapy in Treatment of Human Recurrent Pregnancy Loss

Problem The allogeneic leukocytes in transfused blood can modulate the recipient’s immune system so as to induce TGF‐β‐producing suppressor cells, and the cell‐surface CD200 tolerance‐signaling molecule on mononuclear dendritic cells is required for this effect. A subset of couples with unexplained recurrent pregnancy loss appears to benefit from transfusion of allogeneic paternal blood leukocytes (LIT), and considerable effort has been devoted to characterizing those who may benefit. Some data has been accumulated for LIT as sole therapy in patients with classical spontaneous abortions with respect to dose–response, duration of protection, need for boosting, excluding patients with autoimmunity, and inefficacy of paternal mononuclear cells stored at 4°C overnight before use which causes loss of cell‐surface CD200. Recent data emphasize an important role of expression of the CD200 tolerance‐signaling molecule on cells used to prevent abortions both in mice and humans.Method of study An observational study of outcome as a function of the number of CD200+ paternal mononuclear cells was performed. Fourteen patients constituted the pilot group. Patients with autoimmunity who had failed inspite of treatment with IVIG + Heparin + Aspirin ± Prednisone were allowed to have paternal mononuclear cells added to their therapy. CD200 on purified paternal blood mononuclear cells was measured by flow cytometry.Results The number of CD200+ cells administered was significantly greater in women achieving pregnancy (39.2 × 106 versus 20.8 × 106, P &lt; 0.025) and in those who achieved a live birth (50.2 × 106 versus 20.8 × 106, P &lt; 0.005) compared to those who did not achieve pregnancy, and % of paternal cells that were CD200+ was greater (11–12.5% versus 5.6%, P &lt; 0.01). Amongst those achieving pregnancy which failed, the CD200+ cell dose was not significantly different from the non‐pregnant group (30.5 × 106 versus 20.8 × 106).Conclusion The number of CD200+ paternal mononuclear leukocytes may be an important determinant of subsequent reproductive outcome in a subset of patients. A lower % CD200+ cell number may also reflect hitherto unappreciated paternal factors bearing on reproductive success. It is feasible to recruit women to enter observational studies and to obtain useful data as a foundation for further studies. More complete patient characterization in a larger study is needed.

Laparoscopic Management of Interstitial Pregnancy and Subsequent Reproductive Outcome

Laparoscopic Management of Interstitial Pregnancy and Subsequent Reproductive Outcome

Interstitial Ectopic Pregnancy, Management and Subsequent Reproductive Outcome

Interstitial Ectopic Pregnancy, Management and Subsequent Reproductive Outcome

Cervical pregnancy: A case series and a review of current clinical practice

Five consecutive cases of cervical pregnancy (CP) are presented. In four cases, the diagnosis was made at routine check-ups and these were all treated conservatively. In the fifth case, an erroneous diagnosis of inevitable abortion was made, in a patient presenting with profuse vaginal bleeding. Persistent bleeding following curettage required an emergency hysterectomy, after failure of compressive methods. From the four cases treated conservatively, three received standard methotrexate i.m. (MTX) in combination with bilateral uterine artery embolization (UAE). In one case MTX was followed by intraamniotic puncture and instillation of KCl due to persistent embryonic heartbeat. A spontaneous evacuation of the cervical pregnancy occurred in all patients treated conservatively. We postulate that the preventive use of uterine artery embolization in combination with standard MTX treatment could contribute to reduce the risk of excessive bleeding and facilitate spontaneous expulsion. Possible detrimental effects of the treatment on subsequent reproductive capacities and obstetrical outcome are also pointed out. The diagnostic methods and therapeutic approaches are discussed and the literature is reviewed. With referral to the first case of our series, which required an emergency hysterectomy, we want to stress the importance of an early diagnosis for a correct management of this condition.

The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications.

To evaluate the rate and characteristics of postoperative intrauterine adhesions (IUA) that might be formed following hysteroscopic reproductive surgery from both a gross and a histologic perspective as determined by early and late follow-up diagnostic hysteroscopy. Retrospective analysis of 61 women wishing a pregnancy and suffering from a significant intrauterine pathology affecting their reproductive outcome were reviewed. All patients were treated hysteroscopically. Subsequently, they were randomly assigned to perform a follow-up diagnostic hysteroscopy at a variable intervals from their initial surgery. Multiple hysteroscopic-guided biopsies from IUA, when present, were obtained in several cases. Twenty patients were in the early group and had follow-up hysteroscopy performed 2-4 weeks after the initial operation. The late diagnostic group consisted of 41 patients with follow-up hysteroscopy at about 12 months (8-16 months). The two groups were similar to composition. Postoperatively, none of the early diagnostic group underwent hysterosalpingography (HSG) whereas all of the late group performed HSG 4 months following the initial surgery, which showed at least one-third of the cavity free of adhesions. When adhesions were present, no effort was made to lyse them. At follow-up hysteroscopy, 25% of both groups had no significant adhesions. Grade I adhesions (thin, filmy) occurred in 60% of the early hysteroscopy patients and in only 12% of the late group (P < 0.05). Grade II adhesions were present in 10% of the early group and in up to 41% in the late group (P < 0.05), whereas Grade III adhesions were present in only 5% of the early hysteroscopy group, but in 22% of the late one (P < 0.05). Correlation between hysteroscopic and histologic findings were good in most of cases in both groups. Follow-up to determine the subsequent reproductive outcome revealed similar conception rates in both groups. The IUA that might be formed immediately following hysteroscopic reproductive surgery are histologically different from those appearing a longer time after the original operation. Routine early follow-up hysteroscopy can influence the prognosis resulting from the original surgery.

The effect of passive cigarette smoke on birthweight in pregnant women with asthma

305 306 MATERNAL REPRODUCTIVE OUTCOME FOLLOWING FETAL SURGERY ROBERT WILSON, MARK JOHNSON, LORI HOWELL, ALAN FLAKE, TIM CROMBLEHOLM, HOLLY HEDRICK, SCOTT ADZICK, Children’s Hospital of Philadelphia, Pediatric Surgery, Philadelphia, PA OBJECTIVE: Retrospective database and maternal questionnaire information was used to determine the subsequent reproductive outcome for women following fetal surgery for non-life-threatening and emergency life -threatening fetal disease so that the information may be available for evidence-based presurgical counseling. STUDY DESIGN: The study was approved by the Committee for the Protection of Human Subjects IRB 2003-2-3200. Database review identified 83 women with fetal surgery from a single institution (1996-2002). These women were sent a consent to participate form and a questionnaire looking at postoperative problems, fertility, obstetrical outcomes, and psychosocial concerns . RESULTS: The surgery anomaly in the 83 probands was 52 MMC, 14 thoracic pathology, 13 CDH, and 4 SCT. Present return rate is 46 returned (55% with 2 consent refused), 7 lost to follow-up (8%), and 30 still to be returned. Subsequent pregnancy rate is 47% with 6to 72-month duration and 17% patients having more than one pregnancy. Pregnancy outcome was 33% SA, 6% preterm delivery, and 61% term delivery. Patients with no further pregnancies had sterilization 10% andwanting a further pregnancy in 25%. Complications in a subsequent pregnancy were reported in 5/41 (12%) with uterine rupture at 24 weeks (1), cesarean hysterectomy (1), antepartum hemorrhage requiring transfusion (1), preterm delivery (2) (twin pregnancy; singleton with heart disease). Psychosocial comments re depression and posttraumatic stress following a proband fetal or neonatal death were common in 9 cases returning the questionnaire following loss. CONCLUSION: (1) Spontaneous pregnancy loss is increased over ‘‘quoted’’ 15%-20% background rate. (2) Uterine rupture or dehiscence is similar to classical C section rate (4%-9%). (3) Psychosocial factors for families having fetal surgery need further study. (4) Subsequent pregnancies following fetal surgery have an increased risk for maternal health compared to normal obstetrical population. Volume 189, Number 6 Am J Obstet Gynecol SMFM Abstracts S145

Absence of profound hyperinsulinism in polycystic ovary syndrome is associated with subtle elevations in the plasminogen activator inhibitor system

In order to describe potential hypofibrinolytic tendencies in young (< 35 years) polycystic ovary syndrome (PCOS) patients ,we studied plasminogen activator inhibitor (PAI-1) system components in women without laboratory evidence of hyperinsulinism or hyperandrogenism. The study was a prospective ,observational comparison and took place in a major urban infertility referral center. Age ,body mass index, ovulatory status ,selected androgen levels ,fasting insulin and plasma lipids were measured in subjects with PCOS (n = 39) and normal control subjects (n = 20). Women with PCOS had higher mean serum total testosterone and androstenedione levels compared with controls (56.4 versus 40.3 ng/dl ,p = 0.03 ,and 179 versus 133 μg/ml ,p = 0.03 ,respectively). Mean fasting insulin levels were higher among PCOS women (p < 0.01) and were strongly correlated with PAI-1 antigen (Ag) (r = 0.46) ,PAI-1 activity (r = 0.43) ,and tissue plasminogen activator (t-PA) (r = 0.5). Correlations were evident in both PCOS and control subjects. Mean PAI-1 Ag ,PAI-1 activity ,and t-PA levels were significantly elevated (p = 0.003 ,0.001 ,and 0.001 ,respectively) in PCOS. ANOVA was performed to control for insulin effect; a trend toward elevated PAI-1 in PCOS persisted but was no longer statistically significant (p = 0.24). PAI-1 activity elevation remained in PCOS women with mean fasting insulin levels < 10 mIU/ml (p = 0.02) ,yet the difference became less significant when insulin was controlled (p = 0.38). Although these data confirm known associations between insulin and PAI-1 derangements ,this is the first study to quantify discrete PAI-1 elevations that persist in the setting of PCOS even with normal or low ambient insulin levels. Additional prospective studies are needed to determine whether this altered PAI-1 state is associated with a clinically important hypofibrinolytic condition and subsequent poor reproductive outcome.