Wnt inhibition promotes vascular specification of embryonic cardiac progenitors.

Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSCs). However, few studies have investigated the role of Wnt signaling in the specification of cardiac progenitor cells (CPCs) toward downstream fates. Using transgenic mice and hPSCs, we tracked endothelial cells (ECs) that originated from CPCs expressing NKX2.5. Analysis of EC-fated CPCs at discrete phenotypic milestones during hPSC differentiation identified reduced Wnt activity as a hallmark of EC specification, and the enforced activation or inhibition of Wnt reduced or increased, respectively, the degree of vascular commitment within the CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a, which has been shown to exert an inhibitory influence on Wnt signaling during cardiac development, was dynamically expressed during vascular commitment of hPSC-derived CPCs, and ectopic Wnt5a promoted vascular specification of hPSC-derived and mouse embryonic CPCs.

Natural frozen embryo transfer with hCG booster leads to improved cycle outcomes: a retrospective cohort study.

PURPOSE: To determine whether luteal support with intramuscular injection of human chorionic gonadotropin 1 day post-LH surge in natural cycle frozen embryo transfer (nFETs) increases ongoing pregnancy rates (OPR). METHODS: Retrospective cohort study of women who underwent natural cycle FET with transfer of a single day-5 or - 6 euploid blastocyst between January 2017 and December 2018 at an academic medical center were divided into two groups based on whether they received hCG 1 day post-LH surge. Patients with uterine factor infertility were excluded. RESULTS: A total of 529 nFET cycles were included. The OPR was significantly higher in the treatment group than in the non-treatment group when controlling for potential confounders such as embryo morphology (69.9% versus 57.4%, p = 0.0119, aOR1.724, 95% CI 1.13-2.65). There were no significant differences observed in the rates of first trimester loss (aOR 1.05, 95% CI 0.032-2.96) or biochemical pregnancy (aOR 0.79, 95% CI 0.31-1.76). Odds ratios were adjusted for patient's age, body mass index, peak endometrial thickness, gravidity, and parity. CONCLUSION: The current data suggest that the hCG booster given to patients within 1 day post-LH surge results in improved cycle outcomes compared to patients who do not receive the booster.

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles.

PURPOSE: To investigate the impact of elevated serum estradiol (E2) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles. METHODS: Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E2 levels on day of hCG trigger above or below the 95 % cutoff for E2 values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded. RESULTS: Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E2 levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P = .038). An E2 level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR = 2.29; 95 % CI = 1.03-5.11). The increased odds remained unchanged when adjusting for maternal age (aOR = 2.29; 95 % CI = 1.02-5.14; P = .037), gestational age at delivery (aOR = 2.04; 95 % CI = 1.22-3.98; P = .025), and day 3 versus blastocyst transfer (aOR = 2.5; 95 % CI = 1.11-5.64; P = .023). CONCLUSIONS: Peak E2 level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E2 level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.

Day 3 embryo shape as a morphologic selection parameter in in vitro fertilization.

PURPOSE: To investigate whether embryo shape is a useful morphologic predictor of developmental competence in IVF cycles. METHODS: Two hundred eighteen day 3 single embryo transfer (SET) cycles and 225 day 3 double embryo transfer (DET) cycles in which only 8-cell non-fragmented embryos with symmetric blastomeres were transferred and in which the developmental fate of each embryo was known were analyzed for IVF outcomes with respect to embryo shape. Embryo shape was quantitatively calculated after digitizing embryo images using MATLAB, where a score of 1.0 represented a perfectly circular embryo. RESULTS: The SET data did not reveal a significant impact of embryo shape on embryo developmental fate. The DET data revealed a trend toward the best outcomes in cycles where both embryos exhibited "roundness" scores in the highest tertiles (T3) for embryo shape. However only one subgroup (T2/T1-one embryo in the middle shape tertile (T2) and one in the lowest shape tertile (T1)) was associated with significantly lower odds of live-birth as compared to the referent group (T3/T3). When SET and DET data were combined, embryo shape was not found to be a predictor of IVF outcome. CONCLUSIONS: Based on this retrospective analysis, the weak association of day 3 embryo shape with implantation potential suggests that this morphological characteristic is unlikely to be a useful additional marker for embryo selection after cell number, fragmentation, and blastomere symmetry. Further studies are planned to assess applicability of these conclusions to embryos of varying stages and grades.

Extended in vitro maturation of immature oocytes from stimulated cycles: an analysis of fertilization potential, embryo development, and reproductive outcomes.

PURPOSE: To investigate 24 h in vitro maturation (IVM) of cumulus-stripped immature oocytes from stimulated cycles. METHODS: 263 oocytes identified as immature after cumulus stripping for ICSI were subjected to in vitro maturation (IVM). Fertilization rates and reproductive outcomes of matured oocytes were compared against 234 in vivo matured sibling oocytes (IVO-MII-Sib) from the same cycles (n = 41). Day 2 embryo development was compared against 116 embryos from ICSI cycles having no IVM (IVO-Ext controls). RESULTS: While fertilization rates were similar between IVM and IVO-MII-Sib oocytes (62.1% vs. 64.0%, p = 0.9909), day 2 embryo quality was reduced in the IVM group compared with IVO-Ext controls as evidenced by fewer embryos having 4 cells (28.3% vs. 54.3%, p = 0.0026), low fragmentation (30.0% vs. 65.2%, p < 0.0001) or perfectly symmetric blastomeres (28.6% vs. 46.9%, p = 0.0371). 0 of 17 IVM embryos with known fate implanted. CONCLUSION: Efficacy of 24 h IVM for cumulus-stripped GV and MI oocytes for either clinical use or study of normal meiotic maturation is questionable.

Risk factors for a suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles.

OBJECTIVE: To identify risk factors for a suboptimal response to gonadotropin-releasing hormone (GnRH) agonist trigger in in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): All 424 patients undergoing fresh IVF cycles (n = 500) between August 2007 and June 2013 in whom a GnRH agonist was used as all or part of the ovulation trigger. INTERVENTION(S): GnRH-antagonist-based IVF cycles triggered with leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin. MAIN OUTCOME MEASURE(S): Suboptimal response to GnRH-agonist trigger, as defined by a serum luteinizing hormone (LH) level <15 mIU/mL on the morning after trigger. RESULT(S): The rate of suboptimal response to the GnRH-agonist trigger was 5.2%. Patients with a suboptimal hormone response had lower follicle-stimulating hormone (<0.1 vs. 3.48) and LH (<0.1 vs. 2.51) levels on day 2 of the cycle start, lower LH (0.109 vs. 0.596) on the day of trigger, and required longer stimulation and more gonadotropins than those with an adequate response. Suboptimal responders were also more likely to have irregular menses and be on long-term oral contraception. Patients with an undetectable LH on the day of trigger had a 25% chance of a suboptimal LH surge. In our study cohort, limiting the use of the GnRH-agonist trigger alone to patients with a trigger day LH ≥0.5 would have reduced the rate of suboptimal response from 5.2% to 0.2%. CONCLUSION(S): Long-term hormonal contraception use is an independent risk factor for suboptimal response to GnRH-agonist trigger. Patients with very low endogenous serum LH levels on the day of LH trigger are at increased risk for a suboptimal GnRH-agonist trigger response. Understanding the at-risk phenotype and using trigger day LH as a marker for increased risk of suboptimal GnRH-agonist trigger response can be helpful for individualizing treatment and selecting a safe and efficacious trigger medication for patients undergoing IVF.

Value of antimüllerian hormone as a prognostic indicator of in vitro fertilization outcome.

OBJECTIVE: To determine the predictive attributes of antimüllerian hormone (AMH) in terms of oocyte yield, cycle cancellation, and pregnancy outcomes. DESIGN: Retrospective cohort. SETTING: Academic center. PATIENT(S): All patients initiating IVF at the Weill-Cornell Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine from April 2010 through January 2013. INTERVENTION(S): In vitro fertilization without preimplantation genetic testing. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, cycle cancellation, clinical and ongoing pregnancy, implantation, and miscarriage rates. RESULT(S): Antimüllerian hormone was positively correlated with number of eggs retrieved. Number of oocytes retrieved increased with increasing AMH within each age group and diminished slightly within AMH groupings as age increased. Overall, AMH was significantly correlated with risk of cycle cancellation, with an area under the curve (AUC) of 0.74. Patients with undetectable AMH had a 13.3-fold increased risk of cancellation as compared with patients with an AMH >2.0 ng/mL. Antimüllerian hormone had an AUC of 0.83 for prediction of three or fewer oocytes; undetectable AMH exhibited sensitivity and specificity of 21.1% and 98.2%, respectively, for three or fewer oocytes retrieved. Antimüllerian hormone was less predictive of pregnancy, with AUCs ranging from 0.55 to 0.65. Even with undetectable AMH, 23.5% of patients <40 years old achieved live birth after transfer. CONCLUSION(S): Antimüllerian hormone is a fairly robust metric for the prediction of cancellation and how many oocytes may be retrieved after stimulation but is a relatively poor test for prediction of pregnancy after any given treatment cycle. Patients with extremely low levels of AMH still can achieve reasonable treatment outcomes and should not be precluded from attempting IVF solely on the basis of an AMH value.

Fertility in patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is the most frequently encountered genetic steroid disorder affecting fertility. Steroid hormones play a crucial role in sexual development and reproductive function; patients with either 21- hydroxylase or 11ß-hydroxylase deficiency thus face immense challenges to their fertility. Given the relevance of CAH in reproductive medicine as well as the diagnostic challenges posed by the phenotypic overlap with polycystic ovary syndrome, we review the reproductive pahophysiology of both classic and nonclassic CAH and present contemporary treatment options.

Beyond the American Society for Reproductive Medicine transfer guidelines: how many cleavage-stage embryos are safe to transfer in women ≥43 years old?

OBJECTIVE: To determine the number of cleavage-stage embryos that can be safely transferred in women ≥43 years old. DESIGN: Retrospective cohort. SETTING: Academic medical center. PATIENT(S): All patients ≥43 years old undergoing transfer of five or more cleavage-stage embryos during the period from January 2004 through April 2012. INTERVENTION(S): In vitro fertilization. MAIN OUTCOME MEASURE(S): A total of 567 cycles in 464 patients aged 43-45 years, whose IVF cycles were characterized by transfer of five to eight cleavage-stage embryos were identified. Clinical outcomes and risk of multiples were analyzed, stratifying by age and number of embryos transferred. RESULT(S): Live birth rates per transfer were 14.4%, 9.4%, and 1.3% for women aged 43, 44, and 45 years, respectively. In 43-year-old women, 2.9% (2/69) of pregnancies were triplet gestations (one selective reduction and one spontaneous reduction). Twin birth rate was 16.3%, 6.7%, and 0 (of all live births) for ages 43, 44, and 45 years, respectively. There was no higher order multiple births. Women aged 43 and 44 years having five or more embryos transferred experienced higher clinical pregnancy rates (PRs) than those patients receiving a transfer of three or four embryos. Clinical outcomes for patients undergoing transfer with six or more embryos were not better than those undergoing transfer with five embryos. CONCLUSION(S): Transferring five or more day 3 embryos may be a safe option for patients ≥43 years of age, as it is associated with an overall low rate of multiple gestations. Having more than five embryos available for transfer on day 5 is associated with improved IVF outcomes. Whether this benefit is from the additional embryo(s) for transfer or the inherently better prognosis of such patients remains to be determined.

Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles.

OBJECTIVE: To identify risk factors for breakthrough LH surge despite GnRH antagonist (GnRH-ant) suppression in IVF cycles. DESIGN: Case-control study. SETTING: Academic medical center. PATIENT(S): All patients undergoing IVF from August 2004 through July 2012 in whom GnRH-ant pituitary suppression (0.25 mg/d) was used in a flexible protocol. INTERVENTION(S): GnRH-ant-based IVF. MAIN OUTCOME MEASURE(S): Breakthrough LH surges as evidenced by an increase in LH (minimum 2.5-fold increase from baseline above a threshold of 17 mIU/mL) associated with a decrease in E2, and free fluid on ultrasound. RESULT(S): Breakthrough LH surges despite GnRH-ant administration occurred in 37 (0.34%) of the 10,809 antagonist cycles during the study period. Compared with all patients remaining suppressed, patients with breakthrough surges were significantly older and had significantly increased FSH and decreased antral follicle counts. Compared with age-matched controls (allocation ratio, 1:50), significant differences in ovarian reserve remained evident. CONCLUSION(S): The occurrence of a breakthrough LH surge despite GnRH-ant treatment is a reassuringly rare event. However, patients with diminished ovarian reserve are at risk for this outcome despite GnRH-ant down-regulation. Further studies are needed to determine whether these patients can be prospectively identified and whether they may benefit from higher doses of GnRH-ant.

In vitro fertilization for Orthodox Jewish couples: antagonist cycle modifications allowing for mikveh attendance before oocyte retrieval.

OBJECTIVE: To describe a novel method of altering conventional gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles, thereby allowing for the observance of ritual Jewish practices, and to investigate the impact of these cycle modifications on IVF outcomes. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Orthodox Jewish couples undergoing GnRH antagonist IVF cycles at The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College from January 1, 2007, to November 1, 2011, in whom cycle starts were delayed using GnRH antagonists and estradiol patches. INTERVENTION(S): GnRH antagonist administration on cycle days 2, 3, and 4, as well as estradiol patch application on cycle days 2, 4, and 6. MAIN OUTCOME MEASURE(S): Days of stimulation, total cycle length, implantation, clinical pregnancy, and live-birth rate were compared for 42 Orthodox Jewish couples undergoing a "mikveh patching protocol" versus 42 control patients matched for age, diagnosis, and IVF cycle characteristics. RESULT(S): The protocol modifications successfully ensured the ability to visit the mikveh before retrieval by extending total cycle length by 3.85 days on average, with no decrement in implantation (43.2% vs. 39.3%), clinical pregnancy (57.1% vs. 59.5%), or live-birth rates (50.0% vs. 54.8%) as compared with controls. CONCLUSION(S): GnRH antagonist cycles can be successfully modified to allow for IVF that remains consistent with the observance of Orthodox Jewish practices.

Consecutive gonadotropin-releasing hormone-antagonist in vitro fertilization cycles: does the elapsed time interval between successive treatments affect outcomes?

OBJECTIVE: To determine whether patients who failed an in vitro fertilization (IVF) cycle can proceed with a subsequent IVF cycle after waiting only one menstrual cycle, or whether there is a benefit to allowing two or more menstrual cycles to elapse before proceeding. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): All patients undergoing IVF cycles at The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, from January 1, 2002 to November 1, 2011, in whom two consecutive gonadotropin-releasing hormone (GnRH)-antagonist IVF cycles with identical stimulation protocols took place 35-140 days apart, excluding patients in whom the first cycle resulted in a clinical pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IVF outcomes were compared for 164 patients who initiated a cycle after waiting only one menstrual cycle (35-55 days from previous oocyte retrieval) versus 557 patients waiting two or more menstrual cycles (56-140 days) from their last retrieval before proceeding with their successive cycle start, stratifying for age. RESULT(S): No differences were detected regarding E2 response, oocyte yield, fertilization, or embryo development when comparing patients waiting only one cycle with those waiting two or more cycles, nor were those parameters different when comparing patients' index cycles with their immediate preceding failed cycles. Moreover, clinical outcomes regarding clinical pregnancy, live birth, and cycle cancellation were similar between both study groups. CONCLUSION(S): Delaying successive IVF cycle start for two or more menstrual cycles likely offers no advantage over pursuing repeated IVF after one menstrual cycle.

In vitro fertilization versus conversion to intrauterine insemination in the setting of three or fewer follicles: how should patients proceed when follicular response falls short of expectation?

OBJECTIVE: To determine whether in vitro fertilization (IVF) cycles with suboptimal response should be converted to intrauterine insemination (IUI) or proceed to oocyte retrieval (OR). DESIGN: Retrospective cohort. SETTING: Academic medical center. PATIENT(S): All patients initiating IVF from January 2004 through December 2011. INTERVENTION(S): OR versus conversion to IUI. MAIN OUTCOME MEASURE(S): A total of 1,098 patients were identified whose IVF cycles were characterized by recruitment of three or fewer follicles, excluding patients with bilateral tubal disease or severe male factor. Cycles with three follicles were defined as those with three follicles ≥ 14 mm with no fourth follicle ≥ 10 mm. Cycles with two or fewer follicles were similarly defined. Outcomes were compared for patients proceeding with OR (n = 624) versus converting to IUI (n = 474). Age-adjusted relative risks for pregnancy were calculated, stratifying for number of follicles. RESULT(S): The likelihood of retrieving at least one mature oocyte (82.9% vs. 94.8% vs. 96.2%), having at least one zygote (61.9% vs. 76.8% vs. 84.2%), and undergoing transfer (57.1% vs. 73.0% vs. 83.3%) increased significantly with increasing follicle number. Patients with three or fewer follicles were 2.6 times more likely to achieve a live birth with IVF versus IUI (9.3% vs. 3.4%). This benefit was only apparent when at least two follicles were present. No benefit was gained by performing OR in the setting of one follicle. CONCLUSION(S): IVF compared with IUI presents superior pregnancy rates in the setting of two or more follicles. Assisted reproduction programs may benefit their patients by pursuing IVF in this scenario.

Developmental potential of embryos from intracytoplasmic sperm injection cycles containing fragmented oocytes.

OBJECTIVE: To determine the incidence of fragmented oocytes in intracytoplasmic sperm injection (ICSI) cycles, describe the developmental potential of their sibling oocytes, and define clinical outcomes from affected cycles. DESIGN: Case-control study. SETTING: Academic medical center. PATIENT(S): All ICSI cycles from January 2006 to December 2010 (n = 2,844) were reviewed for the presence of fragmented oocytes at cumulus stripping or fertilization check (n = 93). Sibling oocytes and corresponding embryos from index cycles were compared with matched control cycles without fragmented oocytes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycle characteristics, embryo quality, and pregnancy rates per retrieval. RESULT(S): The incidence of ICSI cycles containing at least one fragmented oocyte was 3.3% (93/2,844). Twelve patients were represented more than once in these 93 index cycles. Only the first cycles (n = 81) were included, of which 28 contained fragmented oocytes at cumulus stripping, 48 at fertilization check, and five at both. Compared with matched controls, index cycles had fewer good-quality embryos available for transfer (18.8% vs. 32.1%) and significantly lower rates of implantation (20.3% vs. 32.7%), clinical pregnancy (33.3% vs. 58.0%), and ongoing delivery (29.6% vs. 49.4%). The cumulative ongoing delivered rate was also significantly lower for index cycles (32.1% vs. 55.6%), with no difference in the percentage of cycles with cryopreserved embryos remaining at study conclusion (13.5% vs. 23.5%). CONCLUSION(S): Cohorts containing fragmented oocytes have decreased developmental potential. The biologic mechanisms underlying this occurrence merit further investigation, and patient counseling should reflect the possible decreased success rates associated with this aberrant developmental pattern.

Fertility preservation using controlled ovarian hyperstimulation and oocyte cryopreservation in a premenarcheal female with myelodysplastic syndrome.

OBJECTIVE: To report the first case of fertility preservation in a premenarcheal female by use of controlled ovarian hyperstimulation and oocyte cryopreservation. DESIGN: Case report. SETTING: Reproductive endocrinology and infertility unit of a tertiary care university-based medical center. PATIENT(S): A 13-year-old premenarcheal female with Tanner stage 3 breast development and Tanner stage 1 pubic hair diagnosed with myelodysplastic syndrome, referred by her medical oncologist for fertility preservation before undergoing a potentially sterilizing antineoplastic therapy. INTERVENTION(S): Evaluation of ovarian reserve, ovarian stimulation, transvaginal oocyte aspiration, in vitro maturation of immature oocytes, and oocyte cryopreservation. MAIN OUTCOME MEASURE(S): Cryopreservation of mature oocytes. RESULT(S): Successful controlled ovarian hyperstimulation allowed for the cryopreservation of 18 mature oocytes before the patient's gonadotoxic treatment. The oocyte retrieval and cryopreservation did not delay the patient's planned chemotherapy. CONCLUSION(S): Ovarian stimulation and oocyte cryopreservation can be successfully performed in premenarcheal/peripubertal patients, thus providing a viable alternative to ovarian tissue freezing for fertility preservation in the pediatric population.

Can in vitro fertilization cycles be salvaged by repeat administration of intramuscular human chorionic gonadotropin the day after failed injection?

OBJECTIVE: To investigate the incidence of negative serum hCG level after initial IM trigger injection and whether such cycles can be salvaged through repeat administration of IM hCG. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): All patients undergoing IVF at the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, from January 1, 2005 to November 1, 2011. INTERVENTION(S): Repeat hCG administration in cases of failed initial trigger. MAIN OUTCOME MEASURE(S): Fertilization, implantation, clinical pregnancy, and live birth rates were analyzed in the index population compared with a control population matched for age, year of cycle start, diagnosis, stimulation protocol, number of prior IVF attempts, oocyte yield, and number of embryos transferred. RESULT(S): The incidence of failed initial IM hCG injection was low, occurring in only 0.25% of the 17,298 fresh IVF cycles at our center during the study period. Of the 41 patients undergoing retrieval who received a second IM injection of hCG approximately 24 hours after the first, the live birth rate was 39.02%. Compared with matched controls, there were no statistical differences in oocyte maturity, fertilization, implantation, clinical pregnancy, or live birth rates. CONCLUSION(S): Although the incidence of failed hCG injection is rare, this study reveals that cycles characterized by incorrect initial administration or failed absorption of hCG can be salvaged by early detection and repeat injection. Assisted reproductive technology (ART) programs may benefit their patients through the assessment of either urine pregnancy tests or measurement of quantitative serum ß-hCG levels before retrieval, thereby preventing empty follicle syndrome.

Prevention of vulvovaginal sequelae in stevens-johnson syndrome and toxic epidermal necrolysis.

Vulvovaginal sequelae of Stevens-Johnson syndrome and toxic epidermal necrolysis are well documented in the literature, although little consensus exists about effective prevention strategies. This review summarizes the available literature and offers expert opinion about how to minimize long-term vaginal impairment from these rare but often devastating illnesses.

Effect of time between human chorionic gonadotropin injection and egg retrieval is age dependent.

OBJECTIVE: To investigate whether egg retrieval at ≥36.5 hours improves IVF outcomes in women aged ≥40 years. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): First-attempt autologous IVF cycles without preimplantation genetic diagnosis, IUI conversion, or intentional delayed egg retrieval were included (n=3,231). Cycles were stratified by age and hCG exposure (<36.5 vs. ≥36.5 hours). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Oocyte yield, maturity, fertilization, embryo quality, implantation, clinical pregnancy, and live birth were analyzed, controlling for age and gonadotropins. Stimulation type, hMG use, stimulation days, day-3 FSH level, and diagnosis were evaluated as potential confounders. Multivariable regression analyses were performed and Wald tests for trend calculated. RESULT(S): No consistent differences in oocyte yield, maturity, fertilization, or embryo quality were detected. No absolute differences in outcomes were noted among group comparisons. However, as age increased, significant trends toward improved implantation, clinical pregnancy, and live birth were detected at ≥36.5 hours. CONCLUSION(S): Extending exposure to hCG for ≥36.5 hours may be beneficial in patients aged≥40 years. A prospective, randomized study is warranted to determine whether retrieval time merits revision for patients of advanced age, as well as the age cutoffs at which such protocols should be applied.

Congenital uterine anomalies affecting reproduction.

The following review seeks to summarise the current data regarding reproductive outcomes associated with congenital uterine anomalies. Such malformations originate from adverse embryologic events ranging from agenesis to lateral and vertical fusion defects. Associated renal anomalies are common both for the symmetric and asymmetric malformations. While fertility is minimally impacted upon by müllerian anomalies in most cases, such malformations have historically been associated with poor obstetric outcomes such as recurrent miscarriage, second trimester loss, preterm delivery, malpresentation and intrauterine foetal demise (IUFD). The following review delineates the existing literature regarding such outcomes and indicates therapies, where applicable, to optimise the care of such patients.