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Ralph S Papas,1 William H Kutteh2,3 1Department of Obstetrics and Gynecology, Saint George Hospital - University Medical Center, Beirut, Lebanon; 2Department of Obstetrics and Gynecology, Baptist Memorial Hospital, Memphis, TN, USA; 3Recurrent Pregnancy Loss Center, Fertility Associates of Memphis, Memphis, TN, USACorrespondence: William H KuttehRecurrent Pregnancy Loss Center, Fertility Associates of Memphis, 80 Humphreys Center, Suite 307, Memphis, TN, 38139, USATel +1 901-747-2229Fax +1 901-747-4446Email wkutteh@fertilitymemphis.comAbstract: Recurrent pregnancy loss (RPL) is an obstetrical complication that affects about 3% of reproductive age couples. Genetic and non-genetic causes of RPL are multiple; however, aneuploidy is the most common obstetrical complication that can explain single and recurrent pregnancy loss (present in about 60% of recognized clinical pregnancies which result in a miscarriage). Parental karyotyping will only be of potential benefit for 2 to 5 percentage of RPL couples who are translocation carriers. Products of conception (POC) karyotype analysis has been used to direct management in RPL and has been shown to be cost-effective, but the technique has many limitations including high culture failure rate and maternal cell contamination. These limitations can be significantly reduced using POC chromosomal microarray (CMA) technology. We believe that POC genetic testing should be performed after the second and subsequent pregnancy loss using CMA. Although the results will not generally alter the course of treatment, the knowledge of the reason for the loss is of great emotional comfort to many patients. In addition, POC CMA performed in conjunction with a regular complete maternal RPL work-up will identify the group of truly unexplained RPL. Thus, only 10% of patients with RPL will complete an evaluation having a euploid loss and an otherwise normal work-up. This group of “truly unexplained RPL” would be ideal for new research trials and therapies. Pre-implantation genetic testing (PGT) technology has improved recently with day 5 trophectoderm biopsy as compared to biopsy on day 3 as well as with the addition of CMA and next-generation sequencing technologies. The most recent studies on PGT-SR (PGT-Structural rearrangement) show improved clinical and live birth rates per pregnancy, as well as decreased miscarriage rate for translocation carriers. PGT-A (PGT-aneuploidy) may have a limited role in RPL in cases with documented recurrent POC aneuploidy.Keywords: karyotype, products of conception, chromosomal microarray analysis, aneuploidy, pre-implantation genetic testing, recurrent pregnancy loss

While insulin-sensitizing agents like metformin have proven useful in managing this disorder, mounting evidence indicates that rosiglitazone can also help induce ovulation and improve the metabolic profile in these patients. [ABSTRACT FROM AUTHOR]

Background: Products of conception samples are often collected and analyzed to try to determine the cause of an early pregnancy loss. However, sample collection may not always be possible, and maternal cell contamination and culture failure can affect the analysis. Cell-free DNA-based analysis of a blood sample could be used as an alternative method in early pregnancy loss cases to detect if aneuploidies were present in the fetus. Methods : In this prospective study, blood samples from early pregnancy loss patients were analyzed for the presence of fetal aneuploidies using a modified version of a noninvasive prenatal testing assay for cell-free DNA analysis. Results from cell-free DNA analysis were compared against the gold standard, microarray analysis of products of conception samples. This study was registered with ClinicalTrials.gov, identifier: NCT04935138. Results : Of the 76 patient samples included in the final study cohort, 11 were excluded from performance calculations. The 65 patient samples included in the final analysis included 49 with an abnormal microarray result and 16 with a normal microarray result. Based on results from these 65 samples, the study found that genome-wide cell-free DNA analysis had a sensitivity of 73.5% with a specificity of 100% for the detection of fetal aneuploidies in early pregnancy loss cases. Conclusions : This prospective study provides further support for the utility of cell-free DNA analysis in detecting fetal aneuploidies in early pregnancy loss cases. This approach could allow for a noninvasive method of investigating the etiology of miscarriages to be made available clinically.

This article considers the addition of comprehensive 24-chromosomal microarray (CMA) analysis of products of conception (POC) to a standard evaluation for recurrent pregnancy loss (RPL) to help direct treatment towards expectant management versus IVF with preimplantation genetic testing for aneuploidies (PGT-A). The review included retrospective data from 65,333 miscarriages, a prospective evaluation of 378 couples with RPL who had CMA testing of POC and the standard workup, and data from an additional 1020 couples who were evaluated for RPL but did not undergo CMA testing of POC. Aneuploidy in POC explained the pregnancy loss in 57.7% (218/378) of cases. In contrast, the full RPL evaluation recommended by the American Society for Reproductive Medicine identified a potential cause in only 42.9% (600/1398). Combining the data from the RPL evaluation and the results of genetic testing of POC provides a probable explanation for the loss in over 90% (347/378) of women. Couples with an unexplained loss after the standard evaluation with POC aneuploidy accounted for 41% of cases; PGT-A may be considered after expectant management. Conversely, PGT-A would have a limited role in those with a euploid loss and a possible explanation after the standard workup. Categorizing a pregnancy loss as an explained versus unexplained loss after the standard evaluation combined with the results of CMA testing of POC may help identify patients who would benefit from expectant management versus PGT-A., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Multiple factors contribute to recurrent pregnancy loss (RPL). This review highlights the latest international guidelines for RPL workup, including immunological testing, by the American Society for Reproductive Medicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE), and the Royal College of Obstetricians and Gynaecologists (RCOG). These three societies recommend testing for antiphospholipid syndrome. ESHRE and RCOG also recommend thyroid peroxidase antibody testing, whereas ASRM does not. All guidelines advise against testing of natural killer cells, cytokines, antinuclear antibodies, human leukocyte antigen (HLA) compatibility, anti-HLA antibodies, and anti-sperm antibodies. However, when following ASRM, ESHRE or RCOG diagnostic guidelines, over 50% of cases have no identifiable cause. Genetic testing of products of conception (POC) can improve our understanding of unexplained RPL as aneuploidy is a common cause of RPL. Based on studies reporting results from chromosomal microarray analysis (CMA) of POC, we propose a novel algorithm for RPL evaluation. The algorithm involves following evidence-based societal guidelines (published by ASRM, ESHRE, or RCOG), excluding parental karyotyping, in combination with CMA testing of miscarriage tissue. When utilizing this new evaluation algorithm, the number of unexplained cases of RPL decreases from over 50% to less than 10%. As a result, most patients are provided an explanation for their loss and healthcare costs are potentially reduced. Patients with an otherwise negative workup with euploid POC, are classified as "truly unexplained RPL". These patients are excellent candidates for enrollment in randomized, controlled trials examining novel immunological testing and treatment protocols., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Preimplantation genetic testing for aneuploidy (PGT-A) is used as a frequent add-on for in-vitro fertilization (IVF) to improve clinical outcomes. The purpose is to select a euploid embryo following chromosomal testing on embryo biopsies. The current practice includes comprehensive chromosome screening (CCS) technology applied on trophectoderm (TE) biopsies. Despite its widespread use, PGT-A remains a controversial topic mainly because all of the RCTs comprised only good prognosis patients with 2 or more blastocysts available; hence the results are not generalizable to all groups of patients. Furthermore, with the introduction of the highly-sensitive platforms into clinical practice (i.e. next-generation sequencing [NGS]), a result consistent with intermediate copy number surfaced and is termed "Mosaic," consistent with a mixture of euploid and aneuploid cells within the biopsy sample. The optimal disposition and management of embryos with mosaic results is still an open question, as many 'mosaics' generated healthy live births with no identifiable congenital anomalies. The present article provides a complete and comprehensive up-to-date review on PGT-A. It discusses in detail the findings of all the published RCTs on PGT-A with CCS, comments on the subject of "mosaicism" and its current management, and describes the latest technique of non-invasive PGT-A.

Research Question: What is the relationship between oocyte donor characteristics and their pain perception, their expectation and experience of pain, and the interaction between pain and overall satisfaction with the donation process?, Design: Institutional Review Board approved, retrospective survey of commercial, US oocyte donors was emailed to recent donors recruited through Donor Egg Bank USA before 2020., Results: Of the 503 opened emails, 246 individuals responded (48.9%). Most donors ranked their pain between minimal and moderate at all time points analysed. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. A high proportion (93.9%) of donors reported being informed of the risk of pain. Those who recalled being informed of the risk of pain were less likely to report higher levels of pain than expected. Although 94.2% of donors reported having an average to positive experience overall, 92.3% (12 out of 13 donors) in the group reporting a negative overall experience said they felt more pain than expected., Conclusions: Donors were well informed about the risk of pain. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. Report of unexpected levels of pain was highly related to low donor satisfaction., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Genetic testing of products of conception (POC) has been proposed as a tool to be used in the evaluation of patients with recurrent pregnancy loss (RPL). Following a complete RPL evaluation, POC results may reveal an aneuploidy and provide an explanation for the miscarriage in more than 55% of cases. When the cytogenetic result of the pregnancy loss reveals a euploid pregnancy, management should be directed towards the identification of treatable abnormalities. Furthermore, the results of POC testing might better define a subgroup of patients with unexplained RPL who may benefit from expectant management versus preimplantation genetics (aneuploid unexplained RPL) or investigational therapy (euploid unexplained RPL)., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium., Methods: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process., Results: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity., Conclusion: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Recurrent pregnancy loss is a distressing pregnancy disorder experienced by ~2.5% of women trying to conceive. Recurrent pregnancy loss is defined as the failure of two or more clinically recognized pregnancies before 20-24 weeks of gestation and includes embryonic and fetal losses. The diagnosis of an early pregnancy loss is relatively straightforward, although progress in predicting and preventing recurrent pregnancy loss has been hampered by a lack of standardized definitions, the uncertainties surrounding the pathogenesis and the highly variable clinical presentation. The prognosis for couples with recurrent pregnancy loss is generally good, although the likelihood of a successful pregnancy depends on maternal age and the number of previous losses. Recurrent pregnancy loss can be caused by chromosomal errors, anatomical uterine defects, autoimmune disorders and endometrial dysfunction. Available treatments target the putative risk factors of pregnancy loss, although the effectiveness of many medical interventions is controversial. Regardless of the underlying aetiology, couples require accurate information on their chances of having a baby and appropriate support should be offered to reduce the psychological burden associated with multiple miscarriages. Future research must investigate the pathogenesis of recurrent pregnancy loss and evaluate novel diagnostic tests and treatments in adequately powered clinical trials.

Purpose of Review: Couples with recurrent pregnancy loss (RPL) are often referred to reproductive specialists to help determine the reason for their repeated losses. This review will help to develop a strategy that is effective in providing a diagnosis, efficient to administer, and cost-effective to the healthcare system., Recent Findings: International societies have published different recommendations for the evaluation of RPL, they consider it appropriate to initiate an evaluation after two (or three) clinical miscarriages. On the contrary, the clinician who follows these guidelines will only be able to offer a possible explanation to fewer than half of the couples being evaluated. Recently, genetic testing of miscarriage tissue using 24-chromosome microarray (CMA) analysis at the time of the second pregnancy loss coupled with testing based on society guidelines has been shown provide an explanation in more than 90% of cases., Summary: New guidelines for the complete evaluation of RPL should consider adding 24-CMA testing on the miscarriage tissue. Providing couples with an explanation for recurrent loss assists them in dealing with the loss and discourages the clinician from instituting unproven therapies. Truly unexplained pregnancy loss can be reduced to less than 10% with this new algorithm. Incorporation of these strategies will result in significant cost savings to the healthcare system.

Purpose: Fertility-related services in pediatric oncology are increasing, but barriers to care remain and few structured programs are described in the literature. Therefore, the study objectives were (1) to characterize fertility-related services in a large pediatric oncology center and (2) to discuss recommendations for fertility-related services across the pediatric cancer continuum., Methods: Medical records of all cases referred to our Fertility Preservation Clinic within a 3-year period were reviewed, which included 292 patients/survivors with malignant disease. Approximately half (n = 152/292, 52.1%) were cancer patients referred prior to treatment (n = 92/152) or while on active therapy (n = 60/152). The other half (n = 140/292; 47.9%) were survivors who had completed treatment., Results: Referrals more than doubled over 3 years. Most patients referred before treatment were offered and opted for FP (72.8% attempted; 58.9% completed). More male than female patients opted for FP (77.6% vs. 22.4%), but completion rates were higher among females (93.3% vs. 76.9%). Rates of FP before treatment did not increase over time (p = .752). Many patients on-treatment were referred for infertility risk counseling, demonstrating information/support needs in this group. Referred survivors questioned their fertility post-treatment and completed fertility assessments, indicating intact fertility among few (~ 15%)., Conclusions: This review demonstrated the acceptance and increasing need for fertility-related services in pediatric oncology across the cancer continuum, including FP before treatment, counseling during treatment, and fertility assessment in survivorship. Based on our experiences, current recommendations are discussed and include standardized procedures, streamlined referrals, adequate communication/education (of providers and families), and meeting specific needs of young cancer patients/survivors.

Objective: To determine the frequency of molar pregnancy in miscarriage cases based on single-nucleotide polymorphism (SNP) microarray testing on products of conception (POC) tissue and to estimate the sensitivity of ultrasound and histopathologic evaluation for cases identified to be at risk for gestational trophoblastic disease., Design: Retrospective cohort analysis., Setting: Reference laboratory., Patient(s): POC specimens from 26,101 consecutive miscarriages., Intervention(s): POC samples were sent to a single laboratory for analysis. Maternal age, gestational age, egg donor use, indication for testing, and additional clinical information were obtained from the requisition form and a survey sent to ordering providers., Main Outcome Measure(s): Rates of full paternal uniparental disomy (UPD), indicative of complete molar pregnancy, and triploidy of paternal origin, indicative of partial molar pregnancy, in POC samples., Result(s): Paternal triploidy was detected in 638 cases (2.8%) and full paternal UPD in 72 cases (0.3%). Of the cases with complete clinical information (224/710; 31.5%), histopathology and/or ultrasound did not detect 71% of partial molar pregnancies and 30% of complete molar pregnancies., Conclusion(s): Molar pregnancy, detected in 3.1% of all miscarriages in this study with the use of 24-chromosome SNP microarray testing, occurred significantly more frequently than previously estimated with the use of ultrasound and/or histopathology., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Problem: Celiac disease (CD) is an autoimmune intestinal inflammatory disease triggered by gluten in the diet. Untreated CD has been associated with pregnancy loss and infertility. The purpose of this study was to screen unselected women with recurrent pregnancy loss (RPL) for markers of CD to determine whether a correlation exists between RPL and CD serum markers., Method of Study: Frequencies of three serum markers of CD [tissue transglutaminase (TTG) IgA, endomysial (EMA) IgA, and deaminated gliadin peptide (DGP) IgA] were determined by enzyme-linked immunoassay (ELISA). Seven hundred and eight women who had two or more failed clinical pregnancies (cases) and one hundred women with at least one live birth and no miscarriages (controls) were included in this study. All cases had a full workup for RPL based on the American Society for Reproductive Medicine 2013 guidelines. Antiphospholipid antibodies (aPL) were correlated with CD markers based on their potential prothrombotic role. Results The results show no significant difference in the prevalence of CD autoantibodies when comparing the RPL patients with the controls. Over half of the patients who tested positive for serum markers for CD also had positive aPL. Conclusion Screening unselected women with RPL who are asymptomatic for CD is not supported based on these data. Women who test positive for CD may be candidates for aPL testing based on the association of adverse pregnancy outcomes., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To describe perceptions of infertility risk among adult survivors of childhood cancer, to test the concordance of survivors' risk perceptions and their adult fertility status, and to identify explanatory factors (sociodemographic factors, gonadotoxic treatments, reproductive history, sexual dysfunction) associated with these outcomes., Patients and Methods: Adult childhood cancer survivors (N = 1,067; without children or a history of pregnancies) completed questionnaires that asked about infertility risk perceptions and participated in physical evaluations, including biomarkers of gonadal functioning (eg, semen analysis, blood hormone levels, menses). Multivariable regression models tested associations between explanatory factors and risk perceptions as well as concordance of perceptions and fertility status., Results: Most childhood cancer survivors (61.9%) perceived themselves at increased risk for infertility, which was significantly associated with sociodemographic factors (older age, white ethnicity, being married/partnered, higher education), gonadotoxic treatments, fertility concerns, previous unsuccessful attempts to conceive, and sexual dysfunction (all P < .05). Laboratory-evaluated impaired gonadal function was found in 24.3% of female and 55.6% of male survivors, but concordance with survivors' risk perceptions was low (Cohen's κ < .19). Most survivors with discordant perceptions overestimated risk (ie, perceived being at risk, though fertility status seemed normal; 19.7% of male and 43.6% of female survivors), whereas a minority underestimated risk (ie, perceived no risk but were impaired/infertile; 16.3% of male and 5.3% of female survivors). Factors related to discordance included sociodemographics, gonadotoxic treatments, fertility concerns, and sexual dysfunction (all P < .05)., Conclusion: Although childfree survivors may correctly consider themselves at risk for infertility on the basis of their previous treatments, such risk perceptions were discordant from laboratory-evaluated fertility status among many survivors in adulthood. Thus, repeated fertility-related communication throughout survivorship is essential, because treatment-indicated risk does not equal fertility status after treatment. Offering fertility testing to those who were at risk and/or those with fertility-related concerns is recommended.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Study Question: Will the addition of 24-chromosome microarray analysis on miscarriage tissue combined with the standard American Society for Reproductive Medicine (ASRM) evaluation for recurrent miscarriage explain most losses?, Summary Answer: Over 90% of patients with recurrent pregnancy loss (RPL) will have a probable or definitive cause identified when combining genetic testing on miscarriage tissue with the standard ASRM evaluation for recurrent miscarriage., What Is Known Already: RPL is estimated to occur in 2-4% of reproductive age couples. A probable cause can be identified in approximately 50% of patients after an ASRM recommended workup including an evaluation for parental chromosomal abnormalities, congenital and acquired uterine anomalies, endocrine imbalances and autoimmune factors including antiphospholipid syndrome., Study Design, Size, Duration: Single-center, prospective cohort study that included 100 patients seen in a private RPL clinic from 2014 to 2017. All 100 women had two or more pregnancy losses, a complete evaluation for RPL as defined by the ASRM, and miscarriage tissue evaluated by 24-chromosome microarray analysis after their second or subsequent miscarriage., Participants/materials, Setting, Methods: Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities, and 24-chromosome microarray evaluation for products of conception (POC); pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; and blood tests for thyroid stimulating hormone (TSH), prolactin and hemoglobin A1c) were evaluated. We excluded cases where there was maternal cell contamination of the miscarriage tissue or if the ASRM evaluation was incomplete. A cost analysis for the evaluation of RPL was conducted to determine whether a proposed procedure of 24-chromome microarray evaluation followed by an ASRM RPL workup (for those RPL patients who had a normal 24-chromosome microarray evaluation) was more cost-efficient than conducting ASRM RPL workups on RPL patients followed by 24-chromosome microarray analysis (for those RPL patients who had a normal RPL workup)., Main Results and the Role of Chance: A definite or probable cause of pregnancy loss was identified in the vast majority (95/100; 95%) of RPL patients when a 24-chromosome pair microarray evaluation of POC testing is combined with the standard ASRM RPL workup evaluation at the time of the second or subsequent loss. The ASRM RPL workup identified an abnormality and a probable explanation for pregnancy loss in only 45/100 or 45% of all patients. A definite abnormality was identified in 67/100 patients or 67% when initial testing was performed using 24-chromosome microarray analyses on the miscarriage tissue. Only 5/100 (5%) patients, who had a euploid loss and a normal ASRM RPL workup, had a pregnancy loss without a probable or definitive cause identified. All other losses were explained by an abnormal 24-chromosome microarray analysis of the miscarriage tissue, an abnormal finding of the RPL workup, or a combination of both. Results from the cost analysis indicated that an initial approach of using a 24-chromosome microarray analysis on miscarriage tissue resulted in a 50% savings in cost to the health care system and to the patient., Limitations, Reasons for Caution: This is a single-center study on a small group of well-characterized women with RPL. There was an incomplete follow-up on subsequent pregnancy outcomes after evaluation, however this should not affect our principal results. The maternal age of patients varied from 26 to 45 years old. More aneuploid pregnancy losses would be expected in older women, particularly over the age of 35 years old., Wider Implications of the Findings: Evaluation of POC using 24-chromosome microarray analysis adds significantly to the ASRM recommended evaluation of RPL. Genetic evaluation on miscarriage tissue obtained at the time of the second and subsequent pregnancy losses should be offered to all couples with two or more consecutive pregnancy losses. The combination of a genetic evaluation on miscarriage tissue with an evidence-based evaluation for RPL will identify a probable or definitive cause in over 90% of miscarriages., Study Funding/competing Interest(s): No funding was received for this study and there are no conflicts of interest to declare., Trial Registration Number: Not applicable.

Purpose To estimate the prevalence of sperm banking among adolescent males newly diagnosed with cancer and to identify factors associated with banking outcomes. Patients and Methods A prospective, single-group, observational study design was used to test the contribution of sociodemographic, medical, psychological/health belief, communication, and developmental factors to fertility preservation outcomes. At-risk adolescent males (N = 146; age 13.00 to 21.99 years; Tanner stage ≥ 3), their parents, and medical providers from eight leading pediatric oncology centers across the United States and Canada completed self-report questionnaires within 1 week of treatment initiation. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs for specified banking outcomes (collection attempt v no attempt and successful completion of banking v no banking). Results Among adolescents (mean age, 16.49 years; standard deviation, 2.02 years), 53.4% (78 of 146) made a collection attempt, with 43.8% (64 of 146) successfully banking sperm (82.1% of attempters). The overall attempt model revealed adolescent consultation with a fertility specialist (OR, 29.96; 95% CI, 2.48 to 361.41; P = .007), parent recommendation to bank (OR, 12.30; 95% CI, 2.01 to 75.94; P = .007), and higher Tanner stage (OR, 5.42; 95% CI, 1.75 to 16.78; P = .003) were associated with an increased likelihood of a collection attempt. Adolescent history of masturbation (OR, 5.99; 95% CI, 1.25 to 28.50; P = .025), banking self-efficacy (OR, 1.23; 95% CI, 1.05 to 1.45; P = .012), and parent (OR, 4.62; 95% CI, 1.46 to 14.73; P = .010) or medical team (OR, 4.26; 95% CI, 1.45 to 12.43; P = .008) recommendation to bank were associated with increased likelihood of sperm banking completion. Conclusion Although findings suggest that banking is underutilized, modifiable adolescent, parent, and provider factors associated with banking outcomes were identified and should be targeted in future intervention efforts.

Study Question: Does lower dose (<26 Gy) cranial radiation therapy (CRT) used for central nervous system prophylaxis in acute lymphoblastic leukemia (ALL) adversely affect sperm concentration or morphology?, Summary Answer: CRT doses <26 Gy had no demonstrable adverse effect on sperm concentration or morphology., What Is Known Already: Treatment with alkylating agents produces oligospermia and azoospermia in some patients. No prior study has been large enough to evaluate the independent effects of alkylating agents and lower dose (<26 Gy) CRT on sperm concentration or morphology., Study Design, Size, Duration: This cross-sectional study included male adult survivors of pediatric ALL who had received alkylating agent chemotherapy with or without CRT and who enrolled in the St. Jude Lifetime Cohort Study (SJLIFE) from September 2007 to October 2013., Participants/materials, Setting, Methods: The inclusion criteria were males, ≥18 years of age, ≥10 years after diagnosis, treated at St. Jude Children's Research Hospital for ALL, and received alkylating agent chemotherapy. Semen analyses were performed on 173 of the 241 (78.1%) adult survivors of pediatric ALL who had received alkylating agent chemotherapy with or without CRT. Cumulative alkylating agent treatment was quantified using the cyclophosphamide equivalent dose (CED). Log-binomial multivariable models were used to calculate relative risks (RRs) and 95% CI., Main Results and the Role of Chance: Compared to those without CRT, risk of oligospermia or azoospermia was not increased for CRT <20 Gy (P = 0.95) or 20-26 Gy (P = 0.58). Participants 5-9 years of age at diagnosis compared to those 0-4 years of age (RR = 1.30, 95% CI, 1.05-.61) or those treated with 8-12 g/m2 CED (RR = 2.06, 95% CI, 1.08-3.94) or ≥12 g/m2 CED (RR = 2.12, 95% CI, 1.09-4.12) compared to those treated with >0 to <4 g/m2 CED had an increased risk for oligospermia or azoospermia., Limitations, Reasons for Caution: Our study relied on the results of one semen analysis. ALL survivors who did not participate in SJLIFE or who declined to submit a semen analysis may also have biased our results regarding the proportion with azoospermia or oligospermia, since those who provided a semen specimen were less likely to have previously fathered children compared to those who did not. The lower rate of previous parenthood among participants may have resulted in a higher observed frequency of azoospermia and oligospermia., Wider Implications of the Findings: Treatment with <26 Gy CRT did not increase the risk of oligospermia or azoospermia, although a CED exceeding 8 g/m2 and an age at diagnosis of 5-9 years did increase risk of oligospermia and azoospermia. These findings can be used to counsel adult survivors of pediatric ALL., Study Funding/competing Interest(s): This work was supported by the National Institutes of Health (grant numbers CA 21765, CA 195547, CA00874) and the American Lebanese Syrian Associated Charities (ALSAC). The authors have no competing interests to declare., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Purpose: The purpose of this study was to examine provider communication and sociodemographic factors which associate with sperm banking outcomes in at-risk adolescents newly diagnosed with cancer., Methods: A prospective single-group quasi-experimental study design was used to test the contributions of provider factors on sperm banking outcomes. Medical providers (N = 52, 86.5% oncologists) and 99 of their at-risk adolescent patients from eight leading pediatric oncology centers in North America completed questionnaires querying provider factors and patient sperm banking outcomes. Logistic regression with single covariates was used to test each provider factor as a potential correlate of the two binary sperm banking study outcomes (collection attempt/no attempt and successful sperm bank/no bank). Multicovariate logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for specified banking outcomes., Results: Fertility referral (OR, 9.01; 95% CI, 2.54-31.90; p < .001) and provider comfort/skills in negotiating barriers to sperm banking with families (OR, 1.94; 95% CI, 1.03-3.63; p < .04) were associated with collection attempts. Adolescents who were referred for a specialized fertility consultation were also almost five times more likely to successfully bank (OR, 4.96; 95% CI, 1.54-16.00; p < .01) compared to those who were not., Conclusions: Provider training in communicating/managing adolescents and their families about sperm banking, and increasing utilization of fertility preservation referrals, should increase the proportion of at-risk males preserving fertility before treatment initiation., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To determine the frequency of subchorionic hematomas (SCH) in first-trimester ultrasound examinations of patients with infertility and recurrent pregnancy loss (RPL) and in patients from a general obstetric population. To determine if the method of assisted reproduction utilized or the use of anticoagulants, such as heparin and aspirin (ASA), influenced frequency of SCH., Design: Prospective, cohort study., Setting: Fertility clinic and general obstetrics clinic., Patient(s): Five hundred and thirty-three women who were pregnant in the first-trimester., Interventions: Not applicable., Main Outcome Measure(s): Frequencies of subchorionic hematomas in women based on diagnosis, use of anticoagulants, and fertility treatment., Result(s): SCH were identified in 129/321 (40.2%) in the study group compared to 23/212 (10.9%) in the control group. Fertility diagnosis and the use of heparin did not appear to affect the frequency of SCH in the first trimester; however, SCH occurred at an almost four-fold increase in patients taking ASA compared to those not taking ASA, regardless of fertility diagnosis or method of fertility treatment., Conclusion(s): The use of ASA may be associated with an increased risk of developing a SCH during the first trimester. The increased frequencies of SCH in pregnancies of patients attending a fertility clinic compared to women from a general obstetrical practice was highly correlated with the use of ASA., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This article discusses the current trends in the diagnosis and treatment of recurrent pregnancy loss. Genetic testing of the miscarriage tissue by 23-chromosome microarray and the ability to identify maternal cell contamination have increased our awareness of the role of aneuploidy as a cause of recurrent pregnancy loss. This increasing influence and the role of genetic testing in developing a strategy for the evaluation of recurrent pregnancy loss are described and discussed. The most common questions that practicing physicians ask about recurrent pregnancy loss include how many losses are needed to make the diagnosis, what counts as a pregnancy loss, what constitutes a full workup, should we get karyotypes on the parents and the miscarriage, and what is the prognosis for a live birth? This review attempts to answer those questions based on current research and clinical experience to expand our current understanding of recurrent pregnancy loss., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The desire to reproduce is one of the strongest human instincts. Many men and women in our society may experience situations that compromise their future fertility. The past several decades have seen an explosion of technologies that have changed the historical limitations regarding fertility preservation. This review offers an overview of the state of the art within fertility preservation including surgical and medical interventions and therapies that necessitate the need for cryopreservation of eggs, sperm, and embryos. The review also addresses the psychological consequences of banking/not banking materials among patients in need of fertility preservation, particularly in the oncofertility context., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recurrent pregnancy loss (RPL) is defined as two or more failed clinical pregnancies before 20 weeks' gestation and may be caused by genetic, endocrinologic, anatomic and immunologic abnormalities. Anatomic uterine anomalies include congenital malformations (bicornuate, didelphic, septate and unicornuate uteri) and acquired defects (fibroids, adenomas, adhesions and polyps). Women with septate and bicornuate uteri, intrauterine adhesions, and some adenomas and fibroids are at increased risk of RPL. Data support surgical treatment of all of these lesions except bicornuate uteri. The role of polyps in RPL is unclear. Minimally invasive options for surgical correction of intrauterine lesions include hysteroscopy, laparoscopy with and without robotic assistance and minilaparotomy.

Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most., (© BMJ Publishing Group Ltd 2015.)

Background: Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer., Methods: We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01-20·3] at diagnosis, 29·0 years [18·4-56·1] at assessment, and a median of 21·0 years [10·5-41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling., Findings: Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m(2) were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=-0·37, p<0·0001). Mean CED was 10 830 mg/m(2) (SD 7274) in patients with azoospermia, 8480 mg/m(2) (4264) in patients with oligospermia, and 6626 mg/m(2) (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m(2) CED for azoospermia (OR 1·22, 95% CI 1·11-1·34), and for oligospermia (1·14, 1·04-1·25), but age at diagnosis and age at assessment were not., Interpretation: Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m(2). Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services., Funding: US National Cancer Institute, American Lebanese Syrian Associated Charities., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose of Review: To review the recent diagnostic criteria, clinical implications, and therapeutic protocols for antiphospholipid antibody syndrome (APS)., Recent Findings: Much has been learned in the recent years concerning the diagnosis of and clinical implications associated with the APS. A number of studies demonstrate some pathophysiologic mechanisms that suggest the impact of antiphospholipid antibodies (APAs) on successful growth and development of the placenta, and ultimately the embryo. These findings are discussed in context with establishing the Bradford Hill criteria for causation between APAs and recurrent pregnancy loss. The recent clinical recommendations from the American Society for Reproductive Medicine and the American College of Obstetrics and Gynecology are included. Practical guidelines for clinicians faced with treating women with antiphospholipid syndrome are presented., Summary: The diagnosis of APS is defined and the clinical treatment protocol recommendations are discussed.

There are few conditions in medicine associated with more heartache to patients than recurrent pregnancy loss (RPL). The management of early RPL is a formidable clinical challenge for physicians. Great strides have been made in characterizing the incidence and diversity of this heterogeneous disorder, and a definite cause of pregnancy loss can be established in more than half of couples after a thorough evaluation. In this review, current data are evaluated and a clear roadmap is provided for the evaluation and treatment of RPL., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Historically, much controversy has existed regarding the association of inherited thrombophilias with adverse pregnancy outcomes. The current guidelines do not recommend screening unless a personal history of venous thromboembolism is present, but the authors' survey of physician screening patterns has suggested that up to 40% of physicians may screen contrary to the current guidelines. This article summarizes the existing evidence for each inherited thrombophilia and reviews the current guidelines., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss. Thus, obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiologic mechanisms of action of aPLs have been described. This article discusses the diagnostic and obstetric challenges of obstetric APS, proposed pathophysiologic mechanisms of APS during pregnancy, and the management of women during and after pregnancy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To determine whether a prior live birth or an increase in number of miscarriages impacted the prevalence of congenital or acquired uterine anomalies in women with predominantly early recurrent miscarriage (RM)., Design: Single-center, cross-sectional study., Setting: Patients with RM at a private practice., Patient(s): Eight hundred seventy-five women who had two or more consecutive miscarriages., Intervention(s): None., Main Outcome Measure(s): Frequencies of congenital uterine anomalies (bicornuate, didelphic, septate, t-shaped, and unicornuate uteri) and acquired uterine anomalies (fibroids, polyps, and adhesions)., Result(s): A uterine anomaly was identified in 169 (19.3%) of the patients. Patients with primary RM were more likely to have congenital anomalies than patients with secondary RM, particularly septa. The occurrence of a prior live birth, however, did not influence the frequency of acquired uterine anomalies, which were detected in equal frequencies in patients with three or more miscarriages when compared with patients with only two miscarriages., Conclusion(s): Although RM patients with a prior viable birth are less likely to have a uterine anomaly than those who have never given birth, our results support a recommendation for diagnostic imaging of the uterus after two losses in women with secondary RM as well as for those with primary RM., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Many male survivors of childhood cancer are at risk for azoospermia. Although both the levels of follicle-stimulating hormone (FSH) and inhibin B are correlated with sperm concentration, their ability to predict azoospermia in survivors of childhood cancer remains uncertain., Patients and Methods: Semen analysis was performed and serum levels of FSH and inhibin B were measured in 275 adult male survivors of childhood cancer who had received gonadotoxic therapy. Receiver operating characteristic (ROC) analysis was performed to determine the optimal inhibin B and FSH values for identifying patients with azoospermia. The patient sample was divided into a learning set and a validation set. Sensitivity, specificity, and positive and negative predictive value were calculated., Results: Inhibin B was dichotomized as ≤ 31 ng/L or more than 31 ng/L and FSH was dichotomized as ≤ 11.5 mIU/mL or more than 11.5 mIU/mL based on results of the ROC analysis. Using these values, the specificity of the serum level of inhibin B for identifying azoospermic survivors was 45.0%, and the positive predictive value was 52.1%. The specificity for FSH was 74.1%, and the positive predictive value was 65.1%., Conclusion: Neither serum inhibin B nor FSH is a suitable surrogate for determination of sperm concentration in a semen sample. Young men and their physicians should be aware of the limitations of these measures for assessment of fertility potential.

The past several decades have seen tremendous advances in the field of medical genetics. The application of genetic technologies to the field of reproductive medicine has ushered in a new era of medicine that is likely to greatly expand in the coming years. Concurrent with an in vitro fertilization (IVF) cycle, it is now possible to obtain a cellular biopsy from a developing embryo and genetically evaluate this sample with increasing sophistication and detail. Preimplantation genetic screening (PGS) is the practice of determining the presence of aneuploidy (either too many or too few chromosomes) in a developing embryo. However, how and in whom PGS should be offered is a topic of much debate.

Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids, a group of inner and outer cell membrane antigens found in mammals. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Although obstetric APS was originally reported in association with slow progressive thrombosis and infarction in the placenta, it is most often associated with a poor obstetric outcome. In fact, obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss (RPL). Thus obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiological mechanisms of action of aPLs have been described. The most common histopathological finding in early pregnancy loss has been defective endovascular decidual trophoblastic invasion. Treatment with heparin and aspirin is emerging as the therapy of choice, with ∼75% of treated women with RPL and aPLs having a successful delivery compared with <50% without treatment. This review highlights the diagnostic challenges of obstetric APS, the obstetric complications associated with APS, proposed pathophysiological mechanisms of APS during pregnancy, and the management of women during and after pregnancy., (© Thieme Medical Publishers.)

Background: Idiopathic secondary recurrent miscarriage may be associated with an abnormal maternal immune response to subsequent pregnancies. Intravenous immunoglobulin (IVIG) has been studied in randomized controlled trials (RCTs) with conflicting results. Therefore, a definitive trial was proposed., Methods: We conducted an investigator-initiated, multicentered, randomized, double-blinded, placebo-controlled trial comparing IVIG with saline in women with idiopathic secondary recurrent miscarriage, defined as a history of at least one prior ongoing pregnancy followed by three or more consecutive unexplained miscarriages. Subjects received either IVIG 500 mg/kg or the equivalent volume of normal saline. Preconception infusions were administered 14-21 days from the projected next menstrual period. With documentation of pregnancy, the subject received the same infusion every 4 weeks until 18-20 weeks of gestation. The primary outcome was an ongoing pregnancy of at least 20 weeks of gestation., Results: A total of 82 patients enrolled, of whom 47 had an index pregnancy. All ongoing pregnancies resulted in live births. Therefore, the live birth rates were 70% (16/23) in the IVIG group and 63% (15/24) in the control group (P = 0.760); odds ratio (OR) 1.37 [95% confidence interval (CI) 0.41-4.61]. Including only clinical pregnancies (embryo with cardiac activity at 6 weeks of gestation), the live birth rates were equivalent, 94% (16/17) and (15/16), respectively (P > 0.999); OR 1.07 (95% CI 0.06-18.62). Meta-analysis of randomized controlled trials (RCTs) evaluating IVIG for idiopathic secondary recurrent miscarriage revealed live birth rates of 70% (31/44) in the IVIG group and 62% (28/45) in the control group (P = 0.503); common OR 1.44 (95% CI 0.59-3.48)., Conclusions: This is the largest RCT to date in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis, which combined our study results with two prior RCTs, also showed no significant effect of treatment with IVIG.

Objective: To determine whether the frequency of abnormal results for evidence-based diagnostic tests differed among women with recurrent pregnancy loss (RPL) based on the number of prior losses (n = 2, 3, or > or =4) and to determine whether abnormal results for additional investigative diagnostic tests differed in prevalence among women with different numbers of pregnancy losses., Design: Single-center, retrospective study., Setting: Patients with RPL at a private practice., Patient(s): One thousand twenty women who had two or more consecutive spontaneous pregnancy losses with the same partner., Intervention(s): None., Main Outcome Measure(s): Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities; pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; thrombophilic tests for the factor V Leiden mutation; and blood tests for thyroid-stimulating hormone [TSH] and fasting blood glucose). We also measured the frequency of abnormal results for nine additional investigative tests in the same patients (antiphosphatidyl serine antibodies, microbial infection, midluteal P, PRL, functional protein C activity, functional protein S activity, antithrombin activity, fasting homocysteine and methylenetetrahydrofolate reductase polymorphisms, and factor II mutation)., Result(s): The prevalence of abnormal results for evidence-based and investigative diagnostic tests did not differ among women with different numbers of pregnancy losses., Conclusion(s): Evaluation of all couples with two, three, or more consecutive miscarriages is recommended., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective. To determine whether CD9 expression on human granulosa cells (GCs) and platelets could predict the success of conventional fertilization of human oocytes during in vitro fertilization (IVF). Methods. Thirty women undergoing IVF for nonmale factor infertility participated. Platelets from venous blood and GCs separated from retrieved oocytes were prepared for immunofluorescence. Flow cytometry quantified the percent of GCs expressing CD9, and CD9 surface density on GCs and platelets. Fertilization rate was determined for the total number of oocytes, and the number of mature oocytes per patient. Correlations tested for significant relationships (P < .05) between fertilization rates and CD9 expression. Results. CD9 surface density on human GCs is inversely correlated with fertilization rate of oocytes (P = .04), but the relationship was weak. Conclusion. More studies are needed to determine if CD9 expression on GCs would be useful for predicting conventional fertilization success during IVF.

Thrombophilia by definition represents acquired and/or genetic conditions that predispose patients to both venous and arterial thromboembolic events. Thrombosis is the most common cause of death worldwide. On the arterial side, myocardial infarction and stroke result in significant morbidity and mortality. Venous thromboembolic events most commonly involve the deep veins of the lower extremity with potential complications of pulmonary emboli. Pregnancy is a hypercoagulable state, and thromboembolism is the leading cause of antepartum and postpartum maternal mortality. With the description by Dahlback in 1993 of a condition initially labeled activated protein C resistance, significant advances have rapidly followed. Activated protein C resistance was linked to an underlying point mutation resulting in coagulation factor V (factor V Leiden). Recent attention has focused on certain inherited thrombophilic factors that may predispose to arterial and/or venous thromboses and their possible association with pregnancy complications, including early pregnancy loss. These include a group of mostly autosomal dominant, inherited gene mutations leading to a hypercoagulable state, such as factor V Leiden G1691A, factor II or prothrombin G20210A, and hyperhomocysteinemia associated with methylenetetrahydrofolate reductase C677T mutation. In addition, deficiencies in protein S, protein C, and antithrombin can lead to a hypercoagulable state. Although some studies of recurrent pregnancy loss patients with a positive test for an inherited thrombophilia are conflicting, a case-control study of untreated recurrent miscarriage patients who were heterozygous for the factor V Leiden mutation revealed a lower success rate than the controls who had a history of idiopathic recurrent miscarriage. With the identification of genetic risk factors, there has been synergistic amplification of thrombotic risk when one has an abnormal gene (e.g., factor V Leiden) plus environmental issues (e.g., pregnancy). Current understanding indicates that a combination of risk factors, including multiple inherited thrombophilic defects associated with secondary hypercoagulable states, have a particularly strong association with adverse pregnancy outcome.

Objective: To give an overview of currently used investigations and treatments offered to women with recurrent pregnancy loss (RPL) and, from an evidence-based point of view, to evaluate the usefulness of these interventions., Design: Ten experts on epidemiologic, genetic, anatomic, endocrinologic, thrombophilic, immunologic, and immunogenetic aspects of RPL discussed methodologic problems threatening the validity of research in RPL during and after an international workshop on the evidence-based management of RPL., Conclusion(s): Most RPL patients have several risk factors for miscarriage, and an extensive investigation for all major factors should always be undertaken. There is an urgent need for agreement concerning the thresholds for detecting what is normal and abnormal, irrespective of whether laboratory tests or uterine abnormalities are concerned. A series of lifestyle factors should be reported in future studies of RPL because they might modify the effect of laboratory or anatomic risk factors. More and larger randomized controlled trials, including trials of surgical procedures, are urgently needed, and to achieve this objective multiple centers have to collaborate. Current meta-analyses evaluating the efficacy of treatments of RPL are generally pooling very heterogeneous patient populations and treatments. It is recommended that future meta-analyses look at subsets of patients and treatment protocols that are more combinable.

Objective: To evaluate the use of low-molecular-weight heparin (LMWH) in combination with low-dose aspirin (LDA) for the treatment of antiphospholipid antibody (APA)-associated recurrent pregnancy loss and to compare the results with the use of unfractionated heparin (UFH) plus LDA., Design: Prospective, controlled, multicenter pilot study., Setting: Two academically based reproductive health centers., Patient(s): Patients with three or more pregnancy losses and positive APA., Intervention(s): Patients were treated with LMWH and LDA (n = 25) or UFH and LDA (n = 25)., Main Outcome Measure(s): Fetal outcome and maternal complications from treatments were compared between the two treatment groups., Result(s): Of the 25 patients in the LMWH group, 21 (84%) delivered a viable infant and 4 (16%) miscarried. Of the 25 patients in the UFH group, 20 (80%) delivered a viable infant and 5 (20%) miscarried. These differences were not statistically significant. No major bleeding episodes occurred during pregnancy or at the time of delivery. No cases of deep venous thrombosis, thrombocytopenia, pre-eclampsia, gestational diabetes, or bone fractures were noted in either of the two groups., Conclusion(s): In this pilot study, the use of LDA in combination with LMWH during pregnancy for the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome seems to be as safe as UFH plus LDA. Large, randomized trials will be required to determine differences in outcome with LMWH and LDA compared with treatment with UFH combined with LDA in this group of patients.