Spontaneous Bilateral Tubal Ectopic Pregnancy in a Low-Risk Patient: A Case Report with Implications for Preoperative Patient Counseling.

Bilateral tubal ectopic pregnancies (BTP) are the rarest form of ectopic pregnancy. They are difficult to diagnose preoperatively, and an evidence-based guideline for management does not exist. In this report, we discuss a 35-year-old patient who presented with suspected right tubal ectopic pregnancy. BTP was diagnosed intraoperatively, and a laparoscopic bilateral salpingectomy was performed without complication. The diagnosis was subsequently confirmed by pathology. This case highlights the importance of patient counseling and comprehensive preoperative planning. Due to the poor presurgical diagnosis of BTP, patient counseling should include the possibility of BTP, appropriate options for management, and potential loss of fertility following treatment. In addition, all cases of suspected ectopic pregnancy necessitate a thorough preoperative investigation of bilateral adnexa and intraoperative inspection of the pelvis.

A case report of an abnormal trend in hCG levels in a pregnancy complicated by ovarian hyperstimulation syndrome.

OBJECTIVE: To present a case of abnormally trending hCG levels due to ovarian hyperstimulation syndrome (OHSS) and to portray the obscurities of this commonly used method for tracking early pregnancies. DESIGN: Case report. SETTING: Outpatient ART facility. PATIENT: A patient who received controlled ovarian hyperstimulation in an ART cycle. INTERVENTION: Supportive care. MAIN OUTCOME MEASURE: hCG level. RESULT: The hCG levels in this patient with OHSS trended in an abnormal fashion, suggesting a failing or ectopic pregnancy, but the patient had a normal intrauterine fetus. CONCLUSION: hCG levels may be falsely low in pregnancies complicated by OHSS.

Correlation between follicular fluid levels of sRAGE and vitamin D in women with PCOS.

PURPOSE: The pro-inflammatory advanced glycation end products (AGEs) and their anti-inflammatory soluble receptors, sRAGE, play a role in the pathogenesis of PCOS. There is a correlation between vitamin D (vit D) and sRAGE in the serum, whereby vit D replacement increases serum sRAGE levels in women with PCOS, thus incurring a protective anti-inflammatory role. OBJECTIVE: This study aims to compare levels of sRAGE, N-carboxymethyl-lysine (CML; one of the AGEs), and 25-hydroxy-vit D in the follicular fluid (FF) of women with or without PCOS, and to evaluate the correlation between sRAGE and 25-hydroxy-vit D in the FF. MATERIAL AND METHODS: Women with (n = 12) or without (n = 13) PCOS who underwent IVF were prospectively enrolled. RESULTS: Women with PCOS had significantly higher anti-Mullerian hormone levels, higher number of total retrieved and mature oocytes, and higher number of day 3 and day 5 embryos formed. Compared to women without PCOS, women with PCOS had significantly lower FF sRAGE levels. In women with PCOS, in women without PCOS, and in all participants together, there was a significant positive correlation between sRAGE and 25-hydroxy-vit D. sRAGE positively correlated with CML in women without PCOS but not in women with PCOS. CONCLUSIONS: In women with PCOS, the low ovarian levels of the anti-inflammatory sRAGE suggest that sRAGE could represent a biomarker and a potential therapeutic target for ovarian dysfunction in PCOS. Whether there is a direct causal relationship between sRAGE and vit D in the ovaries remains to be determined.

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial.

Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathophysiology of polycystic ovary syndrome (PCOS) and may contribute to increased risk of ovarian hyperstimulation syndrome (OHSS) in affected individuals. Vitamin D (VitD) supplementation improves multiple clinical parameters in VitD-deficient women with PCOS and decreases VEGF levels in several other pathologic conditions. Unveiling the basic mechanisms underlying the beneficial effects of vitamin D on PCOS may enhance our understanding of the pathophysiology of this syndrome. It may also suggest a new treatment for PCOS that can improve it through the same mechanism as vitamin D and can be given regardless of vitamin D levels. Therefore, we aimed to explore the effect of VitD supplementation on serum VEGF levels and assess whether changes in VEGF correlate with an improvement in characteristic clinical abnormalities of PCOS. This is a randomized placebo-controlled trial conducted between October 2013 and March 2015. Sixty-eight VitD-deficient women with PCOS were recruited. Women received either 50,000 IU of oral VitD3 or placebo once weekly for 8 weeks. There was a significant decrease in serum VEGF levels (1106.4 ± 36.5 to 965.3 ± 42.7 pg·mL-1; p < 0.001) in the VitD group. Previously reported findings of this trial demonstrated a significant decrease in the intermenstrual intervals, Ferriman-Gallwey hirsutism score, and triglycerides following VitD supplementation. Interestingly, ∆VEGF was positively correlated with ∆triglycerides (R² = 0.22; p = 0.02) following VitD supplementation. In conclusion, VitD replacement significantly decreases serum VEGF levels correlating with a decrease in triglycerides in women with PCOS. This is a novel molecular explanation for the beneficial effects of VitD treatment. It also suggests the need to investigate a potential role of VitD treatment in reducing the incidence or severity of OHSS in VitD-deficient women with PCOS.

Vitamin D Supplementation Decreases TGF-ß1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial.

CONTEXT: There is an abnormal increase in TGF-ß1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-ß1 levels in several diseases including myelofibrosis. OBJECTIVE: The objective of the study was to determine the effect of VD supplementation on TGF-ß1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-ß1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations. DESIGN: This was a prospective, randomized, placebo-controlled trial. SETTING: The study was conducted at an academic-affiliated medical center. PARTICIPANTS: Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015. INTERVENTIONS: Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks. MAIN OUTCOMES MEASURES: Serum TGF-ß1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment. RESULTS: The VD level significantly increased and normalized after VD supplementation (16.3 ± 0.9 [SEM] to 43.2 ± 2.4 ng/mL; P < .01), whereas it did not significantly change after placebo. After the VD supplementation, there was a significant decrease in the following: the interval between menstrual periods (80 ± 9 to 60 ± 6 d; P = .04), Ferriman-Gallwey score (9.8 ± 1.5 to 8.1 ± 1.5; P < .01), triglycerides (138 ± 22 to 117 ± 20 mg/dL; P = .03), and TGF-ß1 to sENG ratio (6.7 ± 0.4 to 5.9 ± 0.4; P = .04). In addition, the ΔTGF-ß1 to sENG ratio was positively correlated with Δtriglycerides (r = 0.59; P = .03). CONCLUSIONS: VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-ß1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-ß drugs.

Cultural Concerns when Counseling Orthodox Jewish Couples for Genetic Screening and PGD.

There is a spectrum of attitudes within the Orthodox Jewish community towards genetic testing and PGD. Increased understanding of the belief systems of the Orthodox Jewish population will enhance the genetic counselors' ability to better serve this unique group of patients. By improving cultural competence, genetic counselors can help patients choose the testing options that they deem appropriate, while simultaneously respecting the patient's belief system.

Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. METHODS: This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. RESULTS: Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p < 0.01). Moreover, FF PlGF correlated positively with number of oocytes retrieved and the ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p < 0.01). CONCLUSIONS: These data provide evidence that FF PlGF correlates with ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

Current Jewish perspectives on maternal identity.

Infertility counseling is a specialized field that will continue to grow in coming years as the impact of infertility and its treatment is documented more in terms of emotional, physical, social and life consequences. We report here on more recent developments in halakha (Jewish law and ethics) that are of importance to Orthodox Jewish infertile couple considering donor gametes or surrogacy. Counselors should anticipate issues that may arise in the future and assist couples in their efforts to address them. Good medical practice values the importance of understanding the patient's individual concerns and values, including the complex psychological, sociological and cultural context in which they experience their infertility. Good counseling anticipates and addresses future problems about which patients might not currently be aware, and requires up-to-date authoritative information.

Successful Same-Cycle Blastocyst Transfer following Laparoscopic Ovarian Detorsion: A Report of Two Cases and Literature Review.

Ovarian stimulation increases the risk of ovarian torsion. During an in vitro fertilization (IVF) cycle, the effects of ovarian torsion on retrieved oocytes and subsequent pregnancy chances are not clear. Moreover, no cases of ovarian torsion occurring following oocyte retrieval but prior to same-cycle embryo transfer have been reported. Such cases present a clinical dilemma with respect to optimal timing of embryo transfer. We report two cases of a 41-year-old and a 32-year-old infertility patients undergoing IVF who were diagnosed with ovarian torsion within several days following oocyte retrieval. Both patients were treated by early laparoscopic evaluation and detorsion followed by day five embryo transfer, resulting in successful pregnancies. Therefore, after prompt laparoscopic ovarian untwisting of a torsed ovary following egg retrieval, embryo transfer may be performed as originally scheduled during the concurrent cycle leading to favorable pregnancy outcomes.

Characterization of women with elevated antimüllerian hormone levels (AMH): correlation of AMH with polycystic ovarian syndrome phenotypes and assisted reproductive technology outcomes.

OBJECTIVE: Serum Antimüllerian hormone (AMH) levels are elevated in polycystic ovarian syndrome and have been shown to be useful in its diagnosis. However, the clinical significance of extremely high AMH levels is understudied. We aimed to characterize a population of women with elevated AMH (>5 ng/mL). STUDY DESIGN: This was a retrospective cohort study of 134 women presenting to our fertility clinic for infertility evaluation and treatment who were found to have random serum AMH over 5 ng/mL. Women were divided into 3 groups according to AMH: 5-10 ng/mL, >10-14 ng/mL, and >14 ng/mL. Endocrine characteristics, polycystic ovarian syndrome (PCOS) phenotypes, fertilization rate, implantation rate, clinical pregnancy, and multiple pregnancy rates were compared between groups. RESULTS: AMH ranged between 5 to 48 ng/mL. Greater than 97% of women with ultrahigh AMH (>10 ng/mL) had PCOS. In addition, women with AMH >10 ng/mL had greater prevalence of polycystic ovarian morphology and oligoamenorrhea than women with AMH 5-10 ng/mL. Moreover, serum AMH correlated positively with luteinizing hormone, total testosterone, and dehydroepiandrosterone sulfate. Furthermore, AMH showed strong predictive ability for the presence of amenorrhea (area under the curve, 0.87; 95% confidence interval, 0.80-0.92; P < .0001). Despite similar age and mean number of transferred embryos, women with AMH >10 ng/mL showed higher rates of ovarian hyperstimulation syndrome and clinical pregnancy rates compared with women with AMH 5-10 ng/mL. CONCLUSION: These data characterize a population of women with elevated AMH levels, demonstrating that the vast majority of women with AMH >10 ng/mL have PCOS. Increased AMH levels correlated with PCOS severity and are associated with greater ovarian stimulation and higher clinical pregnancy rates following assisted reproductive technology.

Addressing the particular recordkeeping needs of infertile Orthodox Jewish couples considering the use of donated eggs.

Infertility counseling is a specialized field that will continue to grow in coming years as the impact of infertility and its treatment is documented more and more in terms of emotional, physical, social and life consequences. Counselors should anticipate issues that may arise in the future and assist couples in their efforts to address them. We report here on recordkeeping issues of possible future concern that should be addressed when Orthodox Jewish couples make use of donor eggs. Good medical practice values the importance of understanding the patient's individual concerns and values, including the complex psychological, sociological and cultural context in which they experience their infertility. Good counseling anticipates and addresses future problems about which patients might not currently be aware.

Angiopoietin-1 and angiopoietin-2 are altered in polycystic ovarian syndrome (PCOS) during controlled ovarian stimulation.

Polycystic ovarian syndrome (PCOS) ovaries are characterized by increased angiogenesis and hypervascularity. While angiopoietin-1 (Ang-1) and its antagonist, angiopoietin-2 (Ang-2), are essential for ovarian function and angiogenesis, the levels of Ang-1 and Ang-2 in PCOS are unknown. This was a prospective cohort study of 14 PCOS women and 14 matched controls undergoing controlled ovarian stimulation (COS). Serum was collected on day 3, hCG and retrieval days. Follicular fluid (FF) was collected on retrieval day. Serum Ang-1 and Ang-2 levels were constant throughout COS, but serum Ang-1 levels were increased at all time points in PCOS women compared with controls (p < 0.05). No differences between groups were found in serum Ang-2 levels or FF Ang-1 levels. However, FF Ang-2 levels were increased almost 2-fold in PCOS women compared with controls (p < 0.01), and correlated positively with number of oocytes retrieved (r = 0.65, p < 0.0001). This study is the first to provide evidence of an alteration in the Ang-1/Ang-2 system in PCOS women. The biological role of Ang-2 in promoting capillary leakage, the increased Ang-2 FF level in PCOS, and its correlation with number of oocytes suggest that Ang-2 may play an important role in the increased risk of ovarian hyperstimulation in PCOS.

Transforming growth factor-ß1 and its receptor soluble endoglin are altered in polycystic ovary syndrome during controlled ovarian stimulation.

OBJECTIVE: To evaluate the relationship between transforming growth factor (TGF)-ß1 and its receptor, soluble endoglin (sENG), in the serum and follicular fluid of women with polycystic ovarian syndrome (PCOS) compared with that of non-PCOS normal ovulating women during controlled ovarian stimulation (COS). DESIGN: Prospective case-control study. SETTING: Academic-affiliated assisted reproductive technology unit. PATIENT(S): Fourteen PCOS and 14 matched non-PCOS control women undergoing COS. INTERVENTION(S): Serum was collected on day 3 (baseline), day of hCG, and day of retrieval. Follicular fluid (FF) was collected on day of oocyte retrieval. ELISA was performed to determine TGF-ß1 and sENG protein levels. MAIN OUTCOME MEASURE(S): Serum and FF levels of TGF-ß1 and sENG. RESULT(S): Serum TGF-ß1 did not change significantly during COS but was increased in PCOS compared with non-PCOS women on day 3 and days of hCG administration and oocyte retrieval. Serum sENG increased after hCG administration only in the non-PCOS control group. In addition, serum sENG was decreased in PCOS compared with non-PCOS control women on the days of hCG and retrieval. Accordingly, the bioavailability of TGF-ß1 (TGF-ß1/sENG ratio) was increased in women with PCOS compared with non-PCOS controls at all three time points. No differences in either factor were noted in FF between groups. CONCLUSION(S): The increased TGF-ß1 bioavailability in PCOS is not only due to increased TGF-ß1 levels but also to decreased levels of its receptor, sENG. These data suggest that increased TGF-ß1 bioavailability may contribute to the pathogenesis of PCOS and its increased risk for ovarian hyperstimulation.

Anti-Müllerian hormone as an independent predictor of twin versus singleton pregnancy in fresh cycles.

This study evaluated anti-Müllerian hormone (AMH) as a possible predictor of twin pregnancy in women undergoing fresh cycles who had more than one embryo transferred. A retrospective study was performed of 139 patients undergoing fresh non-donor cycles which resulted in either singleton or twin pregnancy between 2009 and 2010 in this fertility clinic. Random serum AMH and other clinically relevant variables were compared. For further analysis, the population was stratified by age (<34 and ⩾34 years). Random serum AMH concentrations were 1.4-times greater in women conceiving twins compared with singletons (P=0.03). In women aged ⩾34, the AMH concentration in twins was 1.8-fold greater than singletons (P=0.001). Multivariate analysis demonstrated that AMH was an independent predictor of twins. ROC curve analysis showed that AMH had a significant predictive ability for twin pregnancy in women aged ⩾34 (AUC 0.67, P=0.01). In contrast, in women aged <34, AMH was not different between twin and singleton pregnancies. In summary, random serum AMH is an independent predictor of twin gestation when more than one embryo is transferred in women aged ⩾34. Considering a woman's AMH before transferring more than one embryo may assist in reducing the incidence of twins. Transferring multiple embryos to increase the chance of pregnancy and live birth rate is a common practice among assisted reproduction providers but often results in a high proportion of multiple pregnancies. Identifying factors predictive of multiple pregnancies is of paramount importance for the successful development of strategies to minimize multiple gestations. Anti-Müllerian hormone (AMH) has been shown to be closely correlated with a woman's egg reserve. Aside from the strong association of serum AMH concentration with quantitative ovarian response, serum AMH concentration has been associated with qualitative aspects of assisted reproduction such as embryo quality and pregnancy rates. Our objective was to evaluate AMH as a possible predictor of twin pregnancy in women undergoing fresh cycles who had more than one embryo transferred. Our study included 139 patients undergoing fresh non-donor cycles which resulted in either a singleton or twin pregnancy between 2009 and 2010 in our fertility clinic. Random serum AMH concentrations were compared. For further analysis, the population was divided into two groups (age <34 and ⩾34). AMH concentrations were 1.4-times greater in women conceiving twins compared with singletons. In women aged ⩾34, the AMH concentration in twins was 1.8-fold greater than singleton pregnancies. AMH was an independent predictor of twins with a significant predictive ability for twin pregnancy in women aged ⩾34. In contrast, in women aged <34, AMH was not different between twin and singleton pregnancies. In conclusion, considering a woman's AMH before transferring more than one embryo may assist in reducing the incidence of twins.

Monozygotic Triplets and Dizygotic Twins following Transfer of Three Poor-Quality Cleavage Stage Embryos.

Background. Assisted reproductive technology has been linked to the increased incidence of monozygotic twinning. It is of clinical importance due to the increased risk of complications in multiple pregnancies in general and in monozygotic twins in particular. Case. A 29-year-old female, nulligravida underwent her first IVF cycle. Three poor-quality cleavage stage embryos were transferred resulting in monochorionic triamniotic triplets and dichorionic diamniotic twins. Selective embryo reduction was performed at 12 weeks leaving dichorionic twins. The patient underwent emergency cesarean section due to preterm labor and nonreassuring fetal heart tracing at 30 weeks of gestation. Conclusion. Our case emphasizes that even embryos with significant morphological abnormalities should be considered viable and the possibility of simultaneous spontaneous embryo splitting must be factored into determining number of embryos to transfer.

Understanding culturally motivated requests from Orthodox Jewish women to delay ovulation.

We report here on the cultural reasons motivating some idiosyncratic requests from married Orthodox Jewish women to delay ovulation. Understanding and respecting the patient's individual concerns and religious values, including the complex psychological, sociological and cultural factors that they involve, is part of good medical practice.

Elevated body mass index is associated with lower serum anti-mullerian hormone levels in infertile women with diminished ovarian reserve but not with normal ovarian reserve.

OBJECTIVE: To investigate the association between elevated body mass index (BMI) and ovarian reserve. DESIGN: Cross-sectional study. SETTING: Academic institutions. PATIENT(S): Two hundred ninety women with infertility. Diminished ovarian reserve (DOR) was defined as day 3 FSH>10 IU/L. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Random serum antimullerian hormone (AMH) levels and number of oocytes retrieved during assisted reproductive technology cycle. RESULT(S): Increasing BMI was associated with lower random serum AMH levels in infertile women with DOR but not in women with normal ovarian reserve (NOR). Among women with DOR, mean random serum AMH levels were 33% lower in overweight and obese women compared with women with normal weight. The same association was not true for women with NOR. Out of 290 women evaluated for infertility, 109 women underwent a controlled ovarian hyperstimulation (COH)-IVF cycle. Women with elevated BMI and DOR had lower number of oocytes retrieved compared with women with normal BMI and DOR (6.4±4.3 vs. 9.4±6), an association that was not observed among women with NOR. CONCLUSION(S): Overweight and obese women with DOR as defined by high day 3 serum FSH levels have lower serum AMH levels and number of oocytes retrieved compared with nonobese women with DOR.

Random anti-Müllerian hormone (AMH) is a predictor of ovarian response in women with elevated baseline early follicular follicle-stimulating hormone levels.

OBJECTIVE: To investigate the utility of random anti-Müllerian hormone (AMH) in assessing ovarian response among women with diminished ovarian reserve (DOR) diagnosed by elevated early follicular-phase FSH levels. DESIGN: Retrospective study. SETTING: Academic and academically affiliated assisted reproductive technology (ART) programs. PATIENT(S): Seventy-three women undergoing ART with elevated early follicular FSH levels. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved during ART cycle, number of day 3 embryos, and cycle cancellation and clinical pregnancy rates. RESULT(S): Random AMH levels were strongly correlated with the number of oocytes retrieved during an ART cycle among women with elevated FSH (r=0.55). Women with elevated FSH who had a random serum AMH level of 0.6 ng/mL or higher had twice the number of oocytes retrieved (11±1.3 vs. 5.6±0.6), a greater number of day 3 embryos (5.7±0.9 vs. 3±0.5), and approximately a third of the cycle cancellation rate (14% vs. 41%) compared with women with a random serum AMH below 0.6 ng/mL. The clinical pregnancy rate was also higher among women with a random serum AMH≥0.6 ng/mL (28% vs. 14%), however, the difference was not statistically significant. CONCLUSION(S): A random serum AMH level is useful in setting expectations for ART prognosis in women with elevated early follicular-phase serum FSH levels.