Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance: Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting. Objective: To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing. Design, Setting, and Participants: Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects. Interventions: The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results. Main Outcomes and Measures: The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy. Results: Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% [95% CI, -10.3% to 3.5%]; rate ratio [RR], 0.95 [95% CI, 0.79 to 1.13]; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% [95% CI, -8.2% to 3.5%]; RR, 0.97 [95% CI, 0.83 to 1.14]; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% [95% CI, -10.4% to 2.4%]; RR, 0.94 [95% CI, 0.80 to 1.12]; P = .25). There were no reported adverse events. Conclusions and Relevance: Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03558399.

A multi-centre international study of salivary hormone oestradiol and progesterone measurements in ART monitoring.

RESEARCH QUESTION: Ovarian stimulation during IVF cycles involves close monitoring of oestradiol, progesterone and ultrasound measurements of follicle growth. In contrast to blood draws, sampling saliva is less invasive. Here, a blind validation is presented of a novel saliva-based oestradiol and progesterone assay carried out in samples collected in independent IVF clinics. DESIGN: Concurrent serum and saliva samples were collected from 324 patients at six large independent IVF laboratories. Saliva samples were frozen and run blinded. A further 18 patients had samples collected more frequently around the time of HCG trigger. Saliva samples were analysed using an immunoassay developed with Salimetrics LLC. RESULTS: In total, 652 pairs of saliva and serum oestradiol were evaluated, with correlation coefficients ranging from 0.68 to 0.91. In the European clinics, a further 237 of saliva and serum progesterone samples were evaluated; however, the correlations were generally poorer, ranging from -0.02 to 0.22. In the patients collected more frequently, five out of 18 patients (27.8%) showed an immediate decrease in oestradiol after trigger. When progesterone samples were assessed after trigger, eight out of 18 (44.4%) showed a continued rise. CONCLUSIONS: Salivary oestradiol hormone testing correlates well to serum-based assessment, whereas progesterone values, around the time of trigger, are not consistent from patient to patient.

Does elevated progesterone on day of oocyte maturation play a role in the racial disparities in IVF outcomes?

The aim of this study was to evaluate if premature progesterone elevation on the last day of assisted reproduction technique stimulation contributes to racial disparities in IVF outcome. A total of 3289 assisted reproduction technique cycles were evaluated in Latino, Asian, African American, and white women. Live birth was more likely in white women (42.6%) compared with Asian (34.8%) and African American women (36.3%), but was similar to Latino women (40.7%). In all racial groups, progesterone was negatively associated with live birth and the negative effect of progesterone persisted when adjusting for confounders. Although the effect of elevated progesterone was similar in all racial groups, the prevalence of elevated progesterone differed. Progesterone > 1.5 ng/ml occurred in only 10.6% of cycles in white women compared with 18.0% in Latino and 20.2% in Asian women. Progesterone > 2 ng/ml occurred in only 2.3% of cycles in white women compared with 6.3% in Latino, 5.9% in Asian and 4.4% in African American women. The increased prevalence of premature elevated progesterone persisted when controlling for IVF stimulation parameters. In conclusion, premature progesterone elevation had a negative effect on live birth in all racial groups studied. The prevalence of elevated progesterone was higher in racial minorities.

Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle.

OBJECTIVE: The purpose of this study was to use a validated prediction model to examine whether single embryo transfer (SET) over 2 cycles results in live birth rates (LBR) comparable with 2 embryos transferred (DET) in 1 cycle and reduces the probability of a multiple birth (ie, multiple birth rate [MBR]). STUDY DESIGN: Prediction models of LBR and MBR for a woman considering assisted reproductive technology developed from linked cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System for 2006-2012 were used to compare SET over 2 cycles with DET in 1 cycle. The prediction model was based on a woman's age, body mass index (BMI), gravidity, previous full-term births, infertility diagnoses, embryo state, number of embryos transferred, and number of cycles. RESULTS: To demonstrate the effect of the number of embryos transferred (1 or 2), the LBRs and MBRs were estimated for women with a single infertility diagnosis (male factor, ovulation disorders, diminished ovarian reserve, and unexplained); nulligravid; BMI of 20, 25, 30, and 35 kg/m2; and ages 25, 35, and 40 years old by cycle (first or second). The cumulative LBR over 2 cycles with SET was similar to or better than the LBR with DET in a single cycle (for example, for women with the diagnosis of ovulation disorders: 35 years old; BMI, 30 kg/m2; 54.4% vs 46.5%; and for women who are 40 years old: BMI, 30 kg/m(2); 31.3% vs 28.9%). The MBR with DET in 1 cycle was 32.8% for women 35 years old and 20.9% for women 40 years old; with SET, the cumulative MBR was 2.7% and 1.6%, respectively. CONCLUSION: The application of this validated predictive model demonstrated that the cumulative LBR is as good as or better with SET over 2 cycles than with DET in 1 cycle, while greatly reducing the probability of a multiple birth.

A weighty issue.

Interventions for management of obesity continue to expand. This Views and Reviews article discusses the impact of obesity on in vitro fertilization outcomes and practices and reviews emerging tools for weight management, specifically glucagon-like peptide-1 agents.

The simplified SART embryo scoring system is highly correlated to implantation and live birth in single blastocyst transfers.

OBJECTIVE: Prior studies have validated the ability of the SART embryo scoring system to correlate with outcomes in cleavage stage embryo transfers. However, this scoring system has not been evaluated in blastocyst transfers. The objective of this study was to estimate the correlation between the simplified SART embryo scoring system and ART cycle outcomes in single blastocyst transfers. MATERIALS AND METHODS: All fresh, autologous single blastocyst transfers cycles from a large ART center from 2010 were analyzed. Blastocysts were given a single grade of good, fair, or poor based upon SART criteria which combines the grading of the inner cell mass and trophectoderm. Multiple logistic regression assessed the predictive value of the SART grade on embryo implantation and live birth. RESULTS: Seven hundred seventeen fresh, autologous single blastocyst transfers cycles were included in the analysis. The live birth rate was 52 % and included both elective and non-elective SBT. Chi square analysis showed higher live birth in good grade embryos as compared to fair (p=0.03) and poor (p=0.02). Univariate binary logistic regression analysis demonstrated SART embryo grading to be significantly correlated with both implantation and live birth (p<0.01). This significance persisted when patient age, BMI, and the stage of the blastocyst were controlled for with multiple logistic regression. In five patients with a poor blastocyst score, there were no live births. CONCLUSION: These data demonstrate that the SART embryo scoring system is highly correlated to implantation and live birth in single blastocyst transfers. Patients with a good grade embryo are excellent candidates for a single blastocyst transfer.

Live birth per embryo transfer with next generation sequencing preimplantation genetic testing: an analysis of 26,107 cycles.

The technique and platform used for preimplantation genetic testing for aneuploidy (PGT-A) have undergone significant changes over time. The contemporary technique utilizes trophectoderm biopsy followed by next-generation sequencing (NGS). The goal of this study was to explore the role of PGT-A using NGS technique exclusively in contemporary in vitro fertilization (IVF) practice. For this, we performed a retrospective analysis of a large dataset collected from the Shady Grove Fertility (SGF) multicentre practice. All autologous IVF cycles which were followed by at least one single embryo transfer (ET) (fresh and/or frozen) between January 2017 to July 2020, were included. Our study group included patients who had PGT-A and the control group included patients who did not proceed with PGT-A. The primary outcome was the live birth rate (LBR) per transfer. All age-adjusted LBR was higher in the PGT-A group than the non-PGT-A group (48.9% vs. 42.7%, p < 0.001), except in women <35 years old among single embryo frozen ETs. Similarly, LBR in the PGT-A group was higher in all ages except in women <35 years old (48.7% vs. 41.7%, p < 0.001) when all single embryos fresh and frozen ETs were included. In patients of decreased ovarian reserve, transfer of euploid embryo was associated with higher LBR (46.7% vs. 26.7%, p < 0.001) whereas miscarriages were lower in patients with unexplained infertility (9.3% vs. 11.3%, p = 0.007 and endometriosis (8.9% vs. 11.6%, p < 0.001) following euploid embryo transfer. To conclude, the transfer of euploid embryos tested via NGS PGT-A was associated with improved LBR per transfer in women ≥35 years old.

Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: a randomized clinical trial.

OBJECTIVE: To determine whether vaginal progesterone for programmed endometrial preparation is noninferior to intramuscular progesterone in terms of live birth rates from frozen embryo transfer (FET). DESIGN: Three-armed, randomized, controlled noninferiority trial. SETTING: Multicenter fertility clinic. PATIENT(S): A total of 1,346 volunteer subjects planning vitrified-warmed transfer of high-quality nonbiopsied blastocysts were screened, of whom 1,125 subjects were ultimately enrolled and randomly assigned to treatment. INTERVENTION(S): The subjects were randomly assigned to receive, in preparation for FET, 50 mg daily of intramuscular progesterone (control group), 200 mg twice daily of vaginal micronized progesterone plus 50 mg of intramuscular progesterone every third day (combination treatment), or 200 mg twice daily of vaginal micronized progesterone. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate per vitrified-warmed embryo transfer. The secondary outcomes were a positive serum human chorionic gonadotropin test 2 weeks after FET, biochemical pregnancy loss, clinical pregnancy, clinical pregnancy loss, total pregnancy loss, serum luteal progesterone concentration 2 weeks after FET, and patient's experience and attitudes regarding the route of progesterone administration, on the basis of a survey administered to the subjects between FET and pregnancy test. RESULT(S): A total of 1,060 FETs were completed. The live birth rate was significantly lower in women receiving only vaginal progesterone (27%) than in women receiving intramuscular progesterone (44%) or combination treatment (46%). Fifty percent of pregnancies in women receiving only vaginal progesterone ended in miscarriage. CONCLUSION(S): The live birth rate after vaginal-only progesterone replacement was significantly reduced, due primarily to an increased rate of miscarriage. Vaginal progesterone supplemented with intramuscular progesterone every third day was noninferior to daily intramuscular progesterone, offering an effective alternative regimen with fewer injections. CLINICAL TRIAL REGISTRATION NUMBER: NCT02254577.

Fertility preservation in an oncology patient who presented with positive human chorionic gonadotropin.

OBJECTIVE: To report the case of a woman who presented for fertility preservation before breast cancer treatment who was found to be pregnant with an undesired pregnancy. DESIGN: Case report. SETTING: Single infertility practice. PATIENT: A 28-year-old woman with a new diagnosis of grade 3 invasive ductal carcinoma of the breast was planning to undergo oocyte cryopreservation and was found to be pregnant with an undesired pregnancy. She underwent a medical termination at a gestational age of 5 weeks 4 days. Neither the patient nor her oncology team wished to delay treatment more than was necessary. The physician and patient decided to initiate controlled ovarian hyperstimulation (COH) before her human chorionic gonadotropin (hCG) returned to normal. INTERVENTIONS: COH in the setting of a positive quantitative hCG. MAIN OUTCOME MEASURES: Number of metaphase II (MII) oocytes cryopreserved; doses of Gonal-F and Menopur; serum E2, follicle-stimulating hormone, luteinizing hormone, hCG levels. RESULTS: COH began 7 days after passing the products of conception. Baseline labs demonstrated hCG at 222 mIU/mL, follicle-stimulating hormone at <0.10 mIU/mL, luteinizing hormone at <1.10 mIU/mL, and E2 at 147 pg/mL. She was started on an antagonist protocol with the use of 150 IU Gonal F and 75 IU Menopur. She was triggered on stimulation day 14 with 5,000 U hCG, and her peak E2 was 5,924 pg/mL. She ultimately had 18 oocytes retrieved, 12 of which were MII, one MI, and five germinal vesicle. All were vitrified. CONCLUSIONS: COH can be achieved in the setting of low positive hCG levels with subsequent successful oocyte maturation. The threshold for hCG trigger to be ineffective in the setting of a positive hCG has yet to be determined.

Economic evaluation of highly purified human menotropin or recombinant follicle-stimulating hormone for controlled ovarian stimulation in high-responder patients: analysis of the Menopur in Gonadotropin-releasing Hormone Antagonist Single Embryo Transfer-High Responder (MEGASET-HR) trial.

OBJECTIVE: To determine the cost of achieving a live birth after first transfer using highly purified human menotropin (HP-hMG) or recombinant follicle-stimulating hormone (FSH) for controlled ovarian stimulation in predicted high-responder patients in the Menopur in Gonadotropin-releasing hormone Antagonist Single Embryo Transfer-High Responder (MEGASET-HR) trial. DESIGN: Cost minimization analysis of trial results. SETTING: Thirty-one fertility centers. PATIENTS: Six hundred and nineteen women with serum antimüllerian hormone ≥5 ng/mL. INTERVENTIONS: Controlled ovarian stimulation with HP-hMG or recombinant FSH in a gonadotropin-releasing hormone (GnRH) antagonist assisted reproduction cycle where fresh transfer of a single blastocyst was performed unless ovarian response was excessive whereupon all embryos were cryopreserved and patients could undergo subsequent frozen blastocyst transfer within 6 months of randomization. MAIN OUTCOME MEASURES: Mean cost of achieving live birth after first transfer (fresh or frozen). RESULTS: First-transfer efficacy, defined as live birth after first fresh or frozen transfer, was 54.5% for HP-hMG and 48.0% for recombinant FSH (difference 6.5%). Average cost to achieve a live birth after first transfer (fresh or frozen) was lower with HP-hMG compared with recombinant FSH. For fresh transfers, the cost was lower with HP-hMG compared with recombinant FSH. The average cost to achieve a live birth after first frozen transfer was also lower in patients treated with HP-hMG compared with recombinant FSH. CONCLUSIONS: Treatment of predicted high-responders with HP-hMG was associated with lower cost to achieve a live birth after first transfer compared with recombinant FSH. CLINICAL TRIAL REGISTRATION NUMBER: NCT02554279.

Mature Follicle Count and Multiple Gestation Risk Based on Patient Age in Intrauterine Insemination Cycles With Ovarian Stimulation.

OBJECTIVE: To estimate the risk of a multiple gestation pregnancy in ovarian stimulation intrauterine insemination (IUI) cycles when stratified by patient age and mature follicle number. METHODS: We conducted a retrospective cohort study at a single private practice fertility center of IUI cycles performed from 2004 to 2017. Intervention(s) were ovarian stimulation and IUI if postwash total motile sperm count was more than 8 million. Mature follicles were defined as 14 mm or more as measured on the day of ovulation trigger. Main outcomes and measures were rates of clinical pregnancy and multiple gestation. RESULTS: We identified 24,649 women who underwent a total of 50,473 IUI cycles. Increasing the number of mature follicles from one to five at the time of IUI in women younger than age 38 years increased the clinical pregnancy rate from 14.6% to 21.9% (adjusted odds ratio [aOR] 1.6, 95% CI 1.4-1.9), almost entirely from a marked increase in multiple gestations per cycle from 0.6% to 6.5% (aOR 9.9, 95% CI 6.9-14.2). There was little increase in singleton pregnancies per IUI (14.1-16.4%) regardless of mature follicle number. The per-pregnancy twin and higher-order multiple gestation risk significantly increased (3.9-23.3%, P<.01 and 0.2-10.6%, P<.01, respectively) when comparing one with five mature follicles present at the time of IUI (P<.01). In women younger than age 38 years with more than three follicles present, more than one quarter of all pregnancies were multiples. Similar findings occurred in women aged 38-40 years. In women older than age 40 years, up to four follicles tripled the odds of pregnancy (aOR 3.1, 95% CI 2.1-4.5) while maintaining a less than 12% risk of multiple gestation per pregnancy and a 1.0% absolute risk of multiples. CONCLUSION: Caution should be used in proceeding with IUI after ovarian stimulation when there are more than two mature follicles in women younger than age 40 years owing to the substantially increased risk of multiple gestation without an improved chance of singleton clinical pregnancy.

Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial.

OBJECTIVE: To assess the noninferiority of vaginal P (Endometrin) compared with daily intramuscular P for replacement in programmed vitrified-warmed blastocyst transfer cycles and to assess the noninferiority of vaginal P in combination with intramuscular progesterone every third day compared with daily intramuscular P. DESIGN: Three-arm randomized controlled noninferiority study. To enable early recognition of inferiority if present, an a priori interim analysis was planned and completed once ongoing pregnancy data were available for 50% of the total enrollment goal. The results of this interim analysis are presented here. SETTING: Assisted reproduction technology practice. PATIENT(S): Women undergoing transfer of nonbiopsied high quality vitrified-warmed blastocyst(s) in a programmed cycle. INTERVENTION(S): Vitrified-warmed blastocyst transfer with mode of P replacement determined by randomization to either: (1) 50 mg daily intramuscular P only; (2) 200 mg twice daily vaginal Endometrin; or (3) 200 mg twice daily Endometrin plus 50 mg intramuscular P every 3rd day. MAIN OUTCOME MEASURE(S): Live birth. The primary outcome of this interim analysis was ongoing pregnancy. RESULT(S): A total of 645 cycles were randomly assigned to one of the three treatment arms, received at least one dose of P replacement therapy according to this assignment and underwent vitrified-warmed blastocyst transfer. These cycles were included in the intention-to-treat analysis. The study team, including the statistician, were blinded to the identity of the treatment arms, which were randomly labeled "A," "B," and "C" in the dataset. Ongoing pregnancy occurred in 50%, 47%, and 31% of cycles in arms A, B, and C respectively. Although arm C had an rate of positive hCG equivalent to the other two arms, the rate of pregnancy loss for arm C was significantly higher than for either of the two arms, resulting in a more than one-third lower rate of ongoing pregnancy. There were no statistically significant differences for any outcome tested between arms A and B. Results of a per-protocol analysis were nearly identical to those of the intention-to-treat analysis. On completion of these analyses, arm C was revealed to be the vaginal P only arm. CONCLUSION(S): Relative to regimens inclusive of intramuscular P, vaginal-only P replacement for vitrified-warmed blastocyst transfer results in decreased ongoing pregnancy, due to increased miscarriage, and should be avoided. Randomization to the vaginal-only arm was terminated with these findings. This trial is ongoing to assess the noninferiority of the vaginal plus every 3rd day intramuscular P arm compared with daily intramuscular P in terms of live birth. CLINICAL TRIAL REGISTRATION NUMBER: NLM identifier NCT02254577.

Defining thresholds for abnormal premature progesterone levels during ovarian stimulation for assisted reproduction technologies.

OBJECTIVE: To evaluate methodologies to establish abnormal progesterone (P) levels on the day of trigger for recommending freeze only cycles. DESIGN: Threshold analysis and cost analysis. SETTING: Private ART practice. PATIENT(S): Fresh autologous ART. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Fourteen established statistical methodologies for generating clinical thresholds were evaluated. These methods were applied to 7,608 fresh ART transfer cycles to generate various P thresholds which ranged widely from 0.4 to 3.0 ng/mL. Lower thresholds ranged from 0.4 to 1 ng/mL and classified the majority of cycles as abnormal as well as required very large number needed to treat (NNT) to increase one live birth. Frozen embryo transfer was cost-effective when P was ≥1.5 ng/mL, with 12% of the population having an abnormal test result and an NNT of 13. Statistical and cost-effective thresholds clustered between 1.5 and 2.0 ng/mL. CONCLUSION(S): Statistically significant thresholds for P were demonstrated as low as 0.4 ng/mL but resulted in a very large NNT to increase one live birth. A clinical benefit to a freeze-only approach was demonstrated above P thresholds ranging from 1.5 to 2.0 ng/dL. At these thresholds, elevated P has a demonstrable and clinically significant negative effect and captures a smaller percentage of the patient population at higher risk for fresh transfer failure, thus making freeze-only a cost-effective option.

Freeze-only versus fresh embryo transfer in a multicenter matched cohort study: contribution of progesterone and maternal age to success rates.

OBJECTIVE: To compare implantation and ongoing pregnancy rates in freeze-only versus fresh transfer cycles. DESIGN: Retrospective matched cohort study. SETTING: Not applicable. PATIENT(S): Women selected using a matching algorithm for similar distributions of clinical characteristics for a total of 2,910 cycles (1,455 fresh cohort and 1,455 freeze-only cohort). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation and ongoing pregnancy rates. RESULT(S): Implantation and ongoing pregnancy rates were statistically significantly higher in the freeze-only transfer cohort than in the matched fresh transfer cohort: ongoing pregnancy rate for freeze-only was 52.0% (95% confidence interval [CI], 49.4-54.6) and for fresh was 45.3% (95% CI, 42.7-47.9), odds ratio (OR) 1.31 (95% CI, 1.13-1.51). In a stratified analysis, the odds of ongoing pregnancy after freeze-only transfer were statistically significantly higher for women both above and below age 35 with progesterone concentration >1.0 ng/mL (age ≤35: OR 1.38 [1.11-1.71]; age >35: OR 1.73 [1.34-2.24]). For women with progesterone concentration ≤1.0 ng/mL, no statistically significant difference in freeze-only odds of ongoing pregnancy was observed in either age group. The sensitivity analysis revealed that increasing maternal age alone (regardless of progesterone) trended toward a more beneficial effect of freeze-only cycles. A lower progesterone concentration was associated with statistically significantly higher ongoing pregnancy odds for fresh but not freeze-only cycles. CONCLUSION(S): Freeze-only transfer protocols are associated with statistically significantly higher ongoing implantation and pregnancy rates compared with fresh transfer cycles. This effect is most pronounced for cycles with progesterone >1.0 ng/mL at trigger and may also be stronger for older patients.

Revisiting the progesterone to oocyte ratio.

OBJECTIVE: To critically evaluate the P to oocyte (O) ratio (P/O) in the prediction of live birth in assisted reproductive technology (ART) cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 7,608 fresh autologous ART ET cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Generalized estimating equation (GEE) models and receiver operating characteristic curves assessed the ability of P, O, and the P/O ratio to predict live birth. In univariate GEE models, P, O, and P/O were each associated with live birth. However, in multivariate GEE models, the P/O ratio was not associated with live birth, but P alone was. This suggested that converting P and O into a ratio of P/O was not more helpful than the two independent variables themselves. Measures of overall model fit further suggested that P/O did not increase the predictive ability of the model over P and O alone. Receiver operating characteristic curves using incremental predictors further demonstrated that the P/O provided no incremental improvement in predicting live birth over P and O separately. CONCLUSION(S): These data suggest that P and O have utility in prediction modeling but demonstrate that additional oocytes were not protective from the negative association of P with live birth. There was no incremental improvement related to the P/O ratio specifically for predicting live birth over each variable independently.

Is FMR1 CGG repeat length a predictor of in vitro fertilization stimulation response or outcome?

OBJECTIVE: To study a broad range of FMR1 CGG repeat lengths and assisted reproduction technology (ART) outcomes. DESIGN: Retrospective cohort study. SETTING: Private ART practice. PATIENT(S): Fresh autologous ART stimulation cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Oocyte yield, live birth. RESULT(S): We screened 14,088 fresh autologous ART cycles from 2012 to 2015, of which 4,690 cycles in 3,290 patients met the inclusion criteria. The FMR1 repeat length was statistically significantly but weakly associated with oocyte yield and other markers of ovarian response. The receiver operating characteristic curve analysis suggested extremely limited predictive ability. Moreover, the FMR1 repeat length was not statistically significantly associated with outcomes in multivariable models, including other markers of ovarian reserve. The FMR1 repeat length was not associated with embryo quality or live birth. Only patient age had a strong ability to predict live birth. CONCLUSION(S): The FMR1 repeat length is associated with ART response, but only weakly. It provides no incremental predictive ability beyond the conventionally used predictors, including patient age, antimüllerian hormone concentration, antral follicle count, and follicle-stimulating hormone level. These data suggest a possible role of the FMR1 repeat length within the normal range in ovarian response but demonstrate no clinically relevant indication for testing FMR1 as a predictor of ART outcomes.