The Risk of Congenital Anomalies by Fertility Treatment Modality.

IMPORTANCE: Up to 4% of all births in developed nations involve assisted reproductive technology (ART), along with other fertility treatment modalities. Thus, ART pregnancies constitute an important epidemiologic population with a known increased risk of congenital anomalies. In this review, we summarize current fertility treatment modalities and their associated risk of congenital anomalies. OBJECTIVE: To review the risk of birth defects among pregnancies conceived with ART and other fertility treatments. EVIDENCE ACQUISITION: Articles were obtained from PubMed and the American College of Obstetricians and Gynecologists and American Society of Reproductive Medicine committee opinions. RESULTS: In vitro fertilization has been associated with a 25% to 50% increased risk of birth defects, including abnormalities of these organ systems: cardiovascular (25%-40% of anomalies), genitourinary (10%-60%), gastrointestinal (10%-20%), and musculoskeletal (10%-35%). Although the data are mixed, intracytoplasmic sperm injection has also been found to be associated with an increased risk of defects, particularly hypospadias, when compared with conventional in vitro fertilization. The risk among fresh versus frozen cycles and cleavage stage versus blastocyst transfers remains uncertain. There appears to be no significant added risk with preimplantation genetic testing, although more studies are needed. Ovulation induction with oral agents appears safe and not associated with an increased risk of anomalies. Oocyte cryopreservation also appears safe, but the data are still limited, requiring future investigation. CONCLUSIONS AND RELEVANCE: While the relative risk of birth defects among ART pregnancies is increased when compared with spontaneous conceptions, the absolute risk remains low. There are no standard screening recommendations for ART pregnancies. Per the American College of Obstetricians and Gynecologists, patients who have undergone ART should be counseled regarding the risk of birth defects and available antenatal evaluation, including fetal echocardiogram and detailed ultrasound evaluation.

Increased Risk of Aortic Dissection Associated With Pregnancy in Women With Turner Syndrome: A Systematic Review.

IMPORTANCE: Turner syndrome (TS) is one of the most common chromosomal abnormalities in women. The condition is characterized by gonadal dysgenesis and is associated with structural cardiac abnormalities. Assisted reproductive technology with oocyte donation may be successful but places women with TS at increased risk of aortic dissection and death. OBJECTIVE: To summarize all cases of aortic dissection associated with pregnancy in women with TS and provide guidance regarding the safety of pregnancy. EVIDENCE ACQUISITION: Systematic review of PubMed for reports of women with TS, aortic dissection, and pregnancy. RESULTS: There are 14 total reported cases of aortic dissection associated with pregnancy in women with TS. Ten of these cases occurred during pregnancy or in the first month postpartum. The majority of affected pregnancies resulted from oocyte donation, 2 of which were multiple gestations. Two women had a documented history of hypertension, and 3 pregnancies were complicated by preeclampsia. Bicuspid aortic valve and coarctation of the aorta were the most common associated cardiac anomalies. More than half of women had some degree of aortic dilatation. Two women had no identifiable risk factors. CONCLUSIONS AND RELEVANCE: Women with TS who desire pregnancy must be thoroughly counseled regarding the increased risk of aortic dissection during pregnancy and postpartum. Preconception consultation with maternal-fetal medicine, reproductive endocrinology, and cardiology is necessary along with a comprehensive physical evaluation. If women with TS choose to pursue pregnancy, they require rigorous cardiac monitoring each trimester during pregnancy and postpartum.

Total follicle stimulating hormone dose is negatively correlated with live births in a donor/recipient model with fresh transfer: an analysis of 8,627 cycles from the Society for Assisted Reproductive Technology Registry.

OBJECTIVE: Oocyte donation has optimized our understanding of ovarian stimulation. Increasing the follicle-stimulating hormone (FSH) dose has been shown to adversely affect live birth rates in autologous cycles. Our objective is to assess whether this relationship holds true within the donor/recipient population. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENTS: Data from 2014-2016 included 8,627 fresh donor cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Live birth, clinical pregnancy, and miscarriage rates. RESULTS: The mean donor age ± standard deviation (SD) was 25.8 ± 2.8 years. Donors underwent a median of 16 days (interquartile range [IQR] 12, 19) of stimulation with a median (IQR) total FSH dose and daily dose of 2,350.0 (1,800.0, 3,025.0) and 153.8 (113.2, 205.0) IU, respectively. The live birth rate was 56.7% per transfer. For every 500-unit increase in FSH dose, there was a 3% reduction in the odds of a live birth (odds ratio [OR] 0.97; 95% confidence interval 0.95, 0.99), and a 3% reduction in the odds of a clinical pregnancy (OR 0.97; 95% confidence interval 0.95, 0.99). Days of stimulation and average daily dose were not significantly associated with live birth or clinical pregnancy. No significant association was found between miscarriage rates and total FSH dose, days of stimulation, or average daily dose. CONCLUSION: This is a novel report of a negative association of total FSH dosage on fresh IVF live births, performed in the donor population to control for oocyte source and endometrial receptivity.

Surrogacy Laws in the United States: What Obstetrician-Gynecologists Need to Know.

The first child carried by a surrogate after in vitro fertilization in the United States was born in 1985. Since then, the number of such births has steadily grown. According to the Centers for Disease Control and Prevention, the number of gestational carrier cycles increased from 727 in 1999 to 3,432 in 2013, encompassing more than 18,000 children born over this period. Surrogacy offers an alternative to adoption. However, it also disrupts traditional notions of parentage and gestation and complicates the role of obstetrician-gynecologists (ob-gyns) in helping their patients navigate difficult ethical issues. Surrogacy legislation falls under the jurisdiction of each individual state, which results in a variety of approaches. In this article, we review the legal aspects of surrogacy important for specialist ob-gyns, including select landmark court cases, states' approaches to surrogacy legislation, and unique components of informed consent. We also provide clinical recommendations specific to the United States for working with gestational surrogates and intended parents, spanning preconception, prenatal care, and delivery.

Clinical pregnancy and live birth increase significantly with every additional blastocyst up to five and decline after that: an analysis of 16,666 first fresh single-blastocyst transfers from the Society for Assisted Reproductive Technology registry.

OBJECTIVE: To study the association between the number of blastocysts available and pregnancy outcomes in first fresh autologous single blastocyst transfer cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Patients from the Society for Assisted Reproductive Technology reporting fertility clinics (n=16,666). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of blastocysts and each outcome. RESULT(S): When comparing fresh single blastocyst transfer rates, the odds of a positive pregnancy outcome (CP) increased significantly with each additional supernumerary blastocyst up to five and declined by 2% for every additional blastocyst after five. Similarly, the odds of an LB was 17% higher for each additional blastocyst up to five and declined by 2% for every additional blastocyst after five. There was no significant association between blastocyst number and miscarriage rate. CONCLUSION(S): Odds of positive pregnancy outcomes (CP, LB) increased significantly with every additional blastocyst up to five, but declined after that, in first fresh autologous cycles with single-blastocyst transfer. The decline after five may be explained by a detrimental effect on endometrial receptivity in patients with a large number of oocytes or inadequate selection of the best embryo for transfer based on morphology alone.

Clinical pregnancy (CP) and live birth (LB) increase significantly with each additional fertilized oocyte up to nine, and CP and LB decline after that: an analysis of 15,803 first fresh in vitro fertilization cycles from the Society for Assisted Reproductive Technology registry.

OBJECTIVE: To study the association between the total number of fertilized oocytes available and pregnancy outcomes in first fresh IVF cycles with a single blastocyst transfer. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 15,803 patients from SART reporting fertility clinics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of fertilized eggs and each outcome. RESULT(S): The median number of total oocytes was 15, and the median number of fertilized oocytes was nine. The odds of a clinical pregnancy were 8% higher for each additional fertilized oocyte up to nine (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.07-1.10) and declined by 9% for every additional fertilized oocyte after nine (OR 0.91; 95% CI 0.89-0.94). Similarly, the odds of an LB was 8% higher for every additional fertilized oocyte up to none (OR 1.08; 95% CI 1.06-1.10) and declined by 8% for every additional fertilized oocyte over nine (OR 0.92; 95% CI 0.90-0.94). CONCLUSION(S): Odds of pregnancy outcomes (CP, LB) increase significantly with every additional fertilized oocyte up to nine, and CP and LB decline after that in first fresh autologous cycles with a single blastocyst transfer.

Freezing of all embryos in in vitro fertilization is beneficial in high responders, but not intermediate and low responders: an analysis of 82,935 cycles from the Society for Assisted Reproductive Technology registry.

OBJECTIVE: To assess in vitro fertilization (IVF) and pregnancy outcomes in patients having their first frozen embryo transfer (FET) after a freeze-all cycle versus similar patients having their first fresh embryo transfer (ET). DESIGN: Retrospective cohort study. SETTING: None. PATIENT(S): Registry data on 82,935 patient cycles from the Society for Assisted Reproductive Technology (SART). INTERVENTION(S): All first fresh autologous IVF cycles were analyzed and compared to first FET cycles after a freeze-all first IVF stimulation. The cycles were subdivided into cohorts based upon the number of oocytes retrieved (OR): 1-5 (low), 6-14 (intermediate), and 15+ (high responders). Univariate analyses were performed on cycle characteristics, and multivariable regression analyses were performed on outcome data. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (CPR) and live-birth rate (LBR). RESULTS: Of the 82,935 cycles analyzed, 69,102 patients had their first fresh transfer, and 13,833 had a first FET. High responders were found to have a higher CPR and LBR in the FET cycles compared with the fresh ET cycles (61.5 vs. 57.4%; 52.0 vs. 48.9%). In intermediate responders, both CPR and LBR were higher after fresh ET compared with FET (49.6% vs. 44.2%; 41.2 vs. 35.3%). Similarly, in low responders, CPR and LBR were higher after fresh compared with FET (33.2% vs. 15.9%; 25.9% vs. 11.5%). CONCLUSION(S): A freeze-all strategy is beneficial in high responders but not in intermediate or low responders, thus refuting the idea that freeze-all cycles are preferable for all patients.

How compliant are in vitro fertilization member clinics in following embryo transfer guidelines? An analysis of 59,689 fresh first in vitro fertilization autologous cycles from 2011 to 2012.

OBJECTIVE: To determine whether IVF clinics are compliant with American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) (ASRM/SART) guidelines and assess the multiple pregnancy outcomes according to the number of embryos transferred. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Data from 59,689 fresh first autologous IVF cycles from the 2011-2012 SART registry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Percentage of compliant cycles, multiple pregnancy rate (PR). RESULT(S): Between 2011 and 2012, a total of 59,689 fresh first autologous cycles were analyzed. Among cleavage-stage ET cycles, the noncompliance rate ranged from 10%-27.4% depending on the age group. The multiple PR was significantly increased in noncompliant cycles involving patients <35 years (38.1% vs. 28.7%) and 35-37 years (35.4% vs. 24.5%) compared with compliant cycles. Among blastocyst-stage ET cycles, the highest rate of noncompliance was seen in patients <35 years old (71%), which resulted in a statistically higher multiple PR (48.3% vs. 2.8%) compared with compliant cycles. Far fewer cycles were noncompliant in patients 35-40 years of age. In a subanalysis of compliant cycles, transferring two blastocyst embryos in patients 35-37 years and 38-40 years resulted in a higher live birth rate compared with the transfer of one embryo (50.4% vs. 40.9% and 42.1% vs. 30.0%, respectively) but the multiple PR was also significantly higher (40.5% vs. 1.7% and 34.0% vs. 2.0%, respectively). CONCLUSION(S): Most first fresh autologous IVF cycles performed from 2011-2012 were compliant with ASRM/SART guidelines, except those that involved a blastocyst ET in patients <35 years. Despite compliance, cycles that involved the transfer of >1 embryo resulted in a high multiple PR, whereas noncompliant cycles resulted in an even more remarkable multiple PR for both cleavage and blastocyst-stage embryos. Clinics need to be more compliant with ET limits and ASRM/SART need to consider revising their guidelines to limit the number of blastocyst transfer to one in patients ≤40 years of age undergoing their first IVF cycle. Furthermore, decreasing the number of cleavage-stage embryos transferred in patients ≤40 years of age should also be considered.

Donor oocytes are associated with preterm birth when compared to fresh autologous in vitro fertilization cycles in singleton pregnancies.

OBJECTIVE: To use a national registry to examine the role of oocyte donation on pregnancy outcomes in singleton pregnancies. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Women undergoing autologous cycles and donor oocyte recipients in the United States from 2008-2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm delivery, birth weight <2,500 g, small for gestational age birthweight, perinatal death. RESULT(S): The rates of preterm delivery and low birthweight for all members of this cohort were higher than the US national average. Pregnancies resulting from oocyte donation were significantly more likely to end before 34 weeks' and 37 weeks' gestation (adjusted odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.03-1.64 for 34 weeks' gestation, adjusted OR = 1.28, 95% CI = 1.12-1.46 for 37 weeks' gestation), and to result in infants weighing <2,500 g (adjusted OR = 1.21, 95% CI = 1.02-1.44). However, once gestational age at delivery is accounted for, these infants are actually at decreased risk of having a small for gestational age birthweight (adjusted OR = 0.72, 95% CI = 0.58-0.89) and of perinatal death (adjusted OR = 0.29, 95% CI = 0.09-0.94). CONCLUSION(S): Data from a national cohort indicate that donor oocyte recipients are more likely to deliver preterm when compared with autologous patients. The effect of donor oocyte donation on birthweight is likely a function of an increased rate of preterm delivery among this population.

Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry.

OBJECTIVE: To analyze donor oocyte cycles in the Society for Assisted Reproductive Technology (SART) registry to determine: 1) how many cycles complied with the 2009 American Society for Reproductive Medicine/SART embryo transfer guidelines; and 2) cycle outcomes according to the number of embryos transferred. For donor oocyte IVF with donor age <35 years, the consideration of single-embryo transfer was strongly recommended. DESIGN: Retrospective cohort study of United States national registry information. SETTING: Not applicable. PATIENT(S): A total of 13,393 donor-recipient cycles from 2011 to 2012. INTERVENTION(S): Embryos transferred in donor IVF cycles. MAIN OUTCOME MEASURE(S): Percentage of compliant cycles, multiple pregnancy rate. RESULT(S): There were 3,157 donor cleavage-stage transfers and 10,236 donor blastocyst transfers. In the cleavage-stage cycles, 88% met compliance criteria. The multiple pregnancy rate (MPR) was significantly higher in the noncompliant cycles. In a subanalysis of compliant cleavage-stage cycles, 91% transferred two embryos and only 9% single embryos. In those patients transferring two embryos, the MPR was significantly higher (33% vs. 1%). In blastocyst transfers, only 28% of the cycles met compliance criteria. The MPR was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles). CONCLUSION(S): The majority of donor cleavage-stage transfers are compliant with current guidelines, but the transfer of two embryos results in a significantly higher MPR compared with single-embryo transfer. The majority of donor blastocyst cycles are noncompliant, which appears to be driving an unacceptably high MPR in these cycles.

High Peak Estradiol/Mature Oocyte Ratio Predicts Lower Clinical Pregnancy, Ongoing Pregnancy, and Live Birth Rates in GnRH Antagonist Intracytoplasmic Sperm Injection Cycles.

OBJECTIVE: To define the relationship between peak estradiol (E2)/mature oocyte ratio and pregnancy outcomes in gonadotropin-releasing hormone (GnRH) antagonist intracytoplasmic sperm injection (ICSI) cycles. STUDY DESIGN: Retrospective cohort study in the setting of an academic reproductive medicine practice. Records from 162 fresh, autologous, GnRH antagonist ICSI cycles performed between 2009 and 2012 .were analyzed. The main outcome measures were rates of clinical pregnancy (CPR), ongoing pregnancy (OPR), and live birth (LBR). RESULTS: For the primary analysis, 4 groups were created based on peak E2/mature oocyte ratio (group 1: <200, group 2: 200-300, group 3: 300-400, and group 4: >400 pg/mL/oocyte). After adjusting for age, basal FSH, and the number of mature oocytes, a significantly lower OPR was seen in group 4 as compared to group I (OR 0.15, 95% CI 0.03-0.86; p=0.032) and group 3 (OR 0.17, 95% CI 0.03-0.98; p=0.048), respectively. The adjusted LBR was also significantly lower in group 4 as compared to group 1 (OR 0.15, 95% CI 0.03-0.83; p=0.030). In a secondary analysis, 3 ranges of peak E2/ mature oocyte ratio (<200, 200-400, and >400 pg/ mL/oocyte) were compared between low, normal, and high responders (<6, 6-15, and >15 mature oocytes, respectively). Clinical pregnancy rate, OPR, and LBR were all lower in normal responders when the E2/oocyte ratio exceeded 400 pg/mL/oocyte as compared to <200 pg/mL/oocyte and 200-300 pg/mL/oocyte (CPR 1% vs. 16% and 32%, respectively, p=0.017; OPR 0 vs. 15% and 27%, respectively, p=0.011; and LBR 0 vs. 13% and 26%, respectively, p=0.018). CONCLUSION: Very elevated peak E2/mature oocyte ratio is associated with a lower CPR, OPR, and LBR in fresh, autologous, GnRH antagonist ICSI cycles.

Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh donor/recipient cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry.

OBJECTIVE: To examine the effect of recipient body mass index (BMI) on IVF outcomes in fresh donor oocyte cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 22,317 donor oocyte cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal recipient BMI (18.5-24.9) were used as the reference group. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate (PR), pregnancy loss rate, live birth rate. RESULT(S): Success rates and adjusted odds ratios with 95% confidence intervals for all pregnancy outcomes were most favorable in cohorts of recipients with low and normal BMI, but progressively worsened as BMI increased. CONCLUSION(S): Success rates in recipient cycles are highest in those with low and normal BMI. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMI with respect to clinical pregnancy and live birth rate.

Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008-2010 Society for Assisted Reproductive Technology registry.

OBJECTIVE: To examine the effect of body mass index (BMI) on IVF outcomes in fresh autologous cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 239,127 fresh IVF cycles from the 2008-2010 Society for Assisted Reproductive Technology registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal BMI (18.5-24.9 kg/m(2)) were used as the reference group (REF). Subanalyses were performed on cycles reporting purely polycystic ovary syndrome (PCOS)-related infertility and those with purely male-factor infertility (34,137 and 89,354 cycles, respectively). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, pregnancy loss rate, and live birth rate. RESULT(S): Success rates and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for all pregnancy outcomes were most favorable in cohorts with low and normal BMIs and progressively worsened as BMI increased. Obesity also had a negative impact on IVF outcomes in cycles performed for PCOS and male-factor infertility, although it did not always reach statistical significance. CONCLUSION(S): Success rates in fresh autologous cycles, including those done for specifically PCOS or male-factor infertility, are highest in those with low and normal BMIs. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMIs. More research is needed to determine the causes and extent of the influence of BMI on IVF success rates in other patient populations.

An Update on Surgical versus Expectant Management of Ovarian Endometriomas in Infertile Women.

Ovarian endometriomas are a common manifestation of endometriosis that can represent a more severe stage of the disease. There is much debate over the treatment of these cysts in infertile women, particularly before use of assisted reproductive technologies. Evidence exists that supports surgical excision of ovarian endometriomas, as well as evidence that cautions against surgical intervention. Certain factors need to be examined closely before proceeding with surgery or continuing with expectant management. These include the patient's symptoms, age, ovarian reserve, size and laterality of the cyst, prior surgical treatment, and level of suspicion for malignancy. The most recent evidence appears to suggest that certain patient profiles may benefit from proceeding directly to in vitro fertilization (IVF). These include symptomatic infertile patients, especially those that are older, those that have diminished ovarian reserve, those that have bilateral endometriomas, or those that have had prior surgical treatment. Although endometriomas can be detrimental to the ovarian reserve, surgical therapy may further lower a woman's ovarian reserve. Nevertheless, the presence of an endometrioma does not appear to adversely affect IVF outcomes, and surgical excision of endometriomas does not appear to improve IVF outcomes. Regardless of treatment plan, infertile patients with endometriomas must be counseled appropriately before choosing either treatment path.

Ectopic pregnancy rate increases with the number of retrieved oocytes in autologous in vitro fertilization with non-tubal infertility but not donor/recipient cycles: an analysis of 109,140 clinical pregnancies from the Society for Assisted Reproductive Technology registry.

OBJECTIVE: To study the impact of controlled ovarian stimulation on ectopic pregnancy (EP) rate as a function of the number of oocytes retrieved, using donor IVF cycles as a control. DESIGN: Retrospective cohort study using a large national database. SETTING: Not applicable. PATIENT(S): Data from 109,140 cycles from the 2008-2010 SART registry, including 91,504 autologous cycles and 17,636 donor cycles in patients with non-tubal infertility. INTERVENTION(S): Varying amounts of oocytes retrieved in autologous and donor IVF. MAIN OUTCOME MEASURE(S): Ectopic pregnancy rates. RESULT(S): In autologous cycles, the EP rate significantly increased as oocyte yield increased. This association was not found in oocyte recipients. CONCLUSION(S): In autologous IVF cycles, increasing oocyte yield is correlated with a significantly increased EP rate. This association is not found in oocyte recipients, indicating that the increased EP rate may be due to the supraphysiologic hormone levels achieved with controlled ovarian hyperstimulation.

High Peak Estradiol Predicts Higher Miscarriage and Lower Live Birth Rates in High Responders Triggered with a GnRH Agonist in IVF/ICSI Cycles.

OBJECTIVE: To investigate parameters predictive of pregnancy outcomes in high responders undergoing fresh, autologous, GnRH antagonist IVF/ICSI cycles using a GnRH agonist trigger. STUDY DESIGN: Retrospective cohort study of all patients deemed high-risk for ovarian hyperstimulation syndrome who underwent fresh, autologous IVF/ICSI using a GnRH agonist trigger at an academic fertility center from 2010-2012. RESULTS: A total of 71 first cycles were analyzed. Rates of clinical pregnancy, live birth (LB), and total (clinical plus biochemical) miscarriage (MC) were 52%, 38%, and 25%, respectively. Mean peak estradiol (E2) and the number of oocytes retrieved were 3,701 pg/mL and 15.2, respectively. Peak E2 was significantly higher in those cycles resulting in clinical MC (p = 0.003). After adjusting for age, basal follicle stimulating hormone, and the number of oocytes retrieved, elevated peak E2 remained associated with increased clinical MC (p = 0.029) and trended towards a relationship with higher total MC (p = 0.062). When peak E2 was treated as a binary variable based on the threshold value of > 5,000 pg/mL, peak E2 above this value was associated with a higher rate of clinical MC (OR = 16.14 with 95% CI 1.25-209.35, p = 0.033) and total MC (OR = 6.81 with 95% CI 1.12-41.54, p = 0.037), as well as a lower LB rate (OR = 0.095 with 95% CI 0.01-0.90, p = 0.041). CONCLUSION: Clinicians should recognize most IVF/ICSI patients triggered with a GnRH agonist as inherently in danger of excessively high serum E2 and avoid peak levels > 5,000 pg/mL in order to avoid higher MC and lower LB rates.