Identifying Factors Associated with Discontinuation of Infertility Treatment Prior to Achieving Pregnancy: Results of a Nationwide Survey.

The purpose of this mixed methods, cross-sectional patient survey was to characterize patient experience, to explore the frequency of and reasons for infertility treatment discontinuation and return to infertility treatments. Participants were recruited from United States patient support groups. Participants had received or were receiving ovulation induction (OI) with or without intrauterine insemination (IUI), with or without subsequent in vitro fertilization (IVF), or IVF with no other previous infertility treatment. Live birth was achieved by 62% of participants. Compared with participants treated with OI/IUI only, participants who underwent OI/IUI followed by ≥1 IVF cycle were less likely to consider discontinuing care (64% vs 77%; P = .014) or to discontinue treatment without achieving a pregnancy (40% vs 58%; P = .004). The most commonly cited reasons for treatment discontinuation were financial (62%) and psychological burden/treatment fatigue (58%). Expected versus actual time to pregnancy differed greatly. Continued desire for a child (60%) was the most frequently cited reason for continuing or resuming treatment. Expanded access to treatment, counseling and fostering realistic expectations regarding cumulative time to pregnancy may reduce treatment discontinuation.

Personalized embryo transfer reduces success rates because endometrial receptivity analysis fails to accurately identify the window of implantation.

After more than a decade of increasingly widespread clinical use, personalized embryo transfer guided by endometrial receptivity analysis (ERA) remains controversial and unproven. One key element missing from the historical literature is the recognition that potential benefits from personalized embryo transfer are entirely dependent on the accuracy and predictive value of the ERA test. Results from the first comprehensive clinical trial, designed in a way that allowed independent evaluation of both potential benefits of personalized embryo transfer and the predictive value of the ERA test upon which it is based, were recently published. However, the authors failed to conduct an appropriate analysis or recognize the significance of their results. Here, we present a simple reanalysis of data from this otherwise excellent randomized controlled trial, demonstrating for the first time that the ERA was unable to identify the window of implantation as purported and that, as a result, personalized embryo transfer based on the ERA actually reduced rather than increased the birth rates. Based on these results and the lack of any contradictory evidence, it is our opinion that all clinical use of ERA-guided personalized embryo transfer should be discontinued immediately, outside of a controlled experimental setting with appropriate informed consent of all participating patients.

Changing gender gap and practice patterns in reproductive endocrinology and infertility subspecialists in the United States: a Society for Reproductive Endocrinology and Infertility report.

OBJECTIVE: To identify changes in current practice patterns, salaries, and satisfaction by gender and by years in practice among board-certified reproductive endocrinology and infertility (REI) subspecialists in the United States. DESIGN: Cross-sectional web-based survey including 37 questions conducted by the Society for Reproductive Endocrinology and Infertility. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome measures were total compensation and practice patterns compared by gender and the type of practice. The secondary outcomes included demographics, the number of in vitro fertilization cycles, surgeries performed, and the morale of survey respondents. RESULT(S): There were 370 respondents (48.4% women and 51.4% men). Compared with a similar survey conducted 6 years earlier, a 27% increase in the number of female respondents was observed in this survey. There was a marginally significant trend toward lower compensation for female than male REI subspecialists (17% lower, $472,807 vs. $571,969). The gap was seen for responders with ≥10 years' experience, which is also when there was the largest gap between private and academic practice (mean $820,997 vs, $391,600). Most (77%) felt positively about the current state of the reproductive endocrinology field, and >90% would choose the subspecialty again. CONCLUSION(S): There has been a substantial increase in the number of recent female REI subspecialists showing less disparity in compensation, and the gap appears to be closing. There is an increasing gap in compensation between private and academic practices with ≥5 years of experience. Reproductive endocrinology and infertility remains a high morale specialty.

Recombinant Human Follicle-Stimulating Hormone Alfa Dose Adjustment in US Clinical Practice: An Observational, Retrospective Analysis of a Real-World Electronic Medical Records Database.

Purpose: To determine the pattern of dose adjustment of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) during ovarian stimulation (OS) for assisted reproductive technology (ART) in a real-world setting. Methods: This was an observational, retrospective analysis of data from an electronic de-identified medical records database including 39 clinics in the USA. Women undergoing OS for ART (initiated 2009-2016) with r-hFSH-alfa (Gonal-f® or Gonal-f RFF Redi-ject®) were included. Assessed outcomes were patients' baseline characteristics and dosing characteristics/cycle. Results: Of 33,962 ART cycles, 13,823 (40.7%) underwent dose adjustments: 23.4% with ≥1 dose increase, 25.4% with ≥1 dose decrease, and 8.1% with ≥1 increase and ≥1 decrease. Patients who received dose adjustments were younger (mean [SD] age 34.8 [4.58] years versus 35.9 [4.60] years, p<0.0001) and had lower BMI (25.1 [5.45] kg/m2 versus 25.5 [5.45] kg/m2, p<0.0001) than those who received a constant dose. The proportion of patients with non-normal ovarian reserve was 38.4% for those receiving dose adjustment versus 51.9% for those with a constant dose. The mean (SD) number of dose changes/cycle was 1.61 (0.92) for cycles with any dose adjustment, 1.72 (1.03) for cycles with ≥1 dose increase, 2.77 (1.00) for cycles with ≥1 dose increase and ≥1 decrease (n=2,755), and 1.88 (1.03) for cycles with ≥1 dose decrease. Conclusions: Dose adjustment during OS is common in clinical practice in the USA and occurred more often in younger versus older patients, those with a high versus non-normal ovarian reserve or those with ovulation disorders/polycystic ovary syndrome versus other primary diagnoses of infertility.

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.

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.

Ambient Air Pollution Exposure and Fecundability in Women Undergoing In Vitro Fertilization.

BACKGROUND: Limited research suggests ambient air pollution impairs fecundity but groups most susceptible have not been identified. We studied whether long-term ambient air pollution exposure prior to an in vitro fertilization (IVF) cycle was associated with successful livebirth, and whether associations were modified by underlying infertility diagnosis. METHODS: Data on women initiating their 1st autologous IVF cycle in 2012-13 were obtained from four U.S. clinics. Outcomes included pregnancy, pregnancy loss, and livebirth. Annual average exposure to fine particulate matter (PM2.5), PM10, and nitrogen dioxide (NO2) prior to IVF start were estimated at residential address using a validated national spatial model incorporating land-use regression and universal kriging. We also assessed residential distance to major roadway. We calculated risk ratios (RR) using modified Poisson regression and evaluated effect modification (EM) by infertility diagnosis on additive and multiplicative scales. RESULTS: Among 7,463 eligible participants, 36% had a livebirth. There was a non-significant indication of an association between PM2.5 or NO2 and decreased livebirth and increased pregnancy loss. Near roadway residence was associated with decreased livebirth (RR: 0.96, 95% CI: 0.82, 0.99. There was evidence for EM between high exposure to air pollutants and a diagnosis of diminished ovarian reserve (DOR) or male infertility and decreased livebirth. CONCLUSIONS: Despite suggestive but uncertain findings for the overall effect of air pollution on fecundity, we found a suggestive indication that there may be synergistic effects of air pollution and DOR or male infertility diagnosis on livebirth. This suggests two possible targets for future research and intervention.

Larger oocyte cohorts maximize fresh IVF cycle birth rates and availability of surplus high-quality blastocysts for cryopreservation.

RESEARCH QUESTION: How does oocyte cohort size affect IVF treatment outcomes? DESIGN: Retrospective cohort analysis of 10,193 fresh autologous oocyte retrievals among good-prognosis patients <35 years from 2009 to 2015. The primary outcome was live birth from a fresh transfer; secondary outcomes included cumulative live birth potential from the retrieved cohort and frequency of severe ovarian hyperstimulation syndrome (OHSS). RESULTS: Live birth per fresh transfer increased as the oocyte cohort increased up to 11-15 oocytes, then plateaued. Beyond 15 oocytes, live birth rates from fresh transfer did not decrease, even at the highest oocyte yields. When accounting for the availability of cryopreserved high-quality supernumerary blastocysts, the cumulative number of potential live births per retrieval continued to increase as oocyte yield increased. Rates of severe OHSS increased rapidly with increasing cohort size above 7-10 oocytes when final oocyte maturation was triggered with human chorionic gonadotrophin (HCG), up to nearly 7% of HCG-triggered retrievals of >25 oocytes, but when triggered with gonadotrophin-releasing hormone (GnRH) agonist the severe OHSS rate remained relatively low and stable at approximately 1% even among retrievals of the largest oocyte cohorts. CONCLUSIONS: Live birth rates per fresh embryo transfer are highest among cycles with retrieval of 11 or more oocytes. Larger cohorts are not associated with any decline in fresh transfer birth rates. Total potential births per retrieval continue to increase as the number of retrieved oocytes increases. Rates of OHSS remain relatively low after retrieval of large oocyte cohorts if final maturation is triggered with GnRH agonist rather than HCG.

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.

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.

Diminished ovarian reserve as measured by means of baseline follicle-stimulating hormone and antral follicle count is not associated with pregnancy loss in younger in vitro fertilization patients.

OBJECTIVE: To assess the relationship between diminished ovarian reserve and pregnancy outcomes in a large cohort of women achieving pregnancy through in vitro fertilization (IVF). We evaluated antral follicle count (AFC) and baseline FSH as a measure of ovarian reserve. Secondarily, we assessed whether diminished ovarian reserve was associated with aneuploidy among spontaneous abortions. DESIGN: Retrospective cohort study. SETTING: Multicenter private practice. PATIENT(S): All patients aged 21-44 years undergoing fresh autologous IVF cycles during 2009-2013 that resulted in positive serum hCG with recorded baseline FSH levels. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live births per early pregnancy, biochemical pregnancies, clinical pregnancy losses, and aneuploidy rates in products of conception among pregnancy losses. RESULT(S): A total of 9,489 cycles among 8,214 patients were analyzed. There was no association between live birth and ovarian reserve among pregnant IVF patients under the age of 35 years. Among patients 35 years of age and older, elevated baseline FSH was associated with a higher risk of pregnancy loss, which increased with increasing age. AFC was not significantly associated with pregnancy loss at any age. No associations were found between ovarian reserve measures and aneuploidy in products of conception in age-adjusted analyses, although the power to effectively evaluate this was limited. CONCLUSION(S): Diminished ovarian reserve is not associated with an increase in miscarriage among younger women achieving pregnancy through IVF. Elevated FSH is associated with a higher risk of IVF pregnancy loss among older patients. We found no evidence to confirm that diminished ovarian reserve is associated with increased aneuploidy among spontaneous abortions.

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.

The slow growing embryo and premature progesterone elevation: compounding factors for embryo-endometrial asynchrony.

STUDY QUESTION: Is there an association of progesterone (P4) on the day of trigger with live birth in autologous ART transfer cycles on day 5 versus day 6? SUMMARY ANSWER: P4 had a greater negative effect on live birth in day 6 fresh transfers compared to day 5 fresh transfers. WHAT IS KNOWN ALREADY: Premature P4 elevation is associated with lower live birth rates in fresh autologous ART cycles, likely due to worsened endometrial-embryo asynchrony. Few studies have evaluated whether the effect of an elevated P4 on the day of trigger is different on live birth rates with a day 5 compared to a day 6 embryo transfer. STUDY DESIGN SIZE, DURATION: This was a retrospective cohort study with autologous IVF cycles with fresh embryo transfers on day 5 and day 6 from 2011 to 2014. A total of 4120 day 5 and 230 day 6 fresh autologous embryo transfers were included. The primary outcome was live birth, defined as a live born baby at 24 weeks gestation or later. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients from a large private ART practice were included. Analysis was performed with generalized estimating equations (GEE) modeling and receiver operating characteristic (ROC) curves. MAIN RESULTS AND THE ROLE OF CHANCE: Day 6 transfers were less likely to have good quality embryos (73% versus 83%, P < 0.001) but the cohorts had similar rates of blastocyst stage transfer (92% versus 91%, P = 0.92). Live birth was less likely in fresh day 6 versus day 5 embryo transfers (34% versus 46%, P = 0.01) even when controlling for embryo confounders. In adjusted GEE models, the effect of P4 as a continuous variable on live birth was more pronounced on day 6 (P < 0.001). Similarly, the effect of P4 > 1.5 ng/ml on day of trigger was more pronounced on day 6 than day 5 (P < 0.001). Day 6 live birth rates were 8% lower than day 5 when P4 was in the normal range (P = 0.04), but became 17% lower when P4 was > 1.5 ng/ml (P < 0.01). ROC curves for P4 predicting live birth demonstrated a greater AUC in day 6 transfers (AUC 0.59, 95% CI 0.51-0.66) than day 5 (AUC 0.54, 95% CI 0.52-0.55). Interaction testing of P4 × day of embryo transfer was highly significant (P < 0.001), further suggesting that the effect of P4 was more pronounced on day 6 embryo transfer. In fresh oocyte retrieval cycles with elevated P4, a subsequent 760 frozen-thaw transfers did not demonstrate a difference between embryos that were frozen after blastulation on day 5 versus 6. LIMITATIONS REASONS FOR CAUTION: Limitations include the retrospective design and the inability to control for certain confounding variables, such as thaw survival rates between day 5 and day 6 blastocysts. Also, the data set lacks the known ploidy status of the embryos and the progesterone assay is not currently optimized to discriminate between patients with a P4 of 1.5 versus 1.8 ng/ml. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests further endometrial-embryo asynchrony when a slow growing embryo is combined with an advanced endometrium, ultimately leading to decreased live births. This suggests that premature elevated P4 may be a factor in the lower live birth rates in day 6 fresh embryo transfers. Further studies are needed to evaluate if a frozen embryo transfer cycle can ameliorate the effect of elevated P4 on the day of trigger among these slower growing embryos that reach blastocyst staging on day 6. STUDY FUNDING/COMPETING INTERESTS: No external funding was received for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Assessing the adequacy of gonadotropin-releasing hormone agonist leuprolide to trigger oocyte maturation and management of inadequate response.

OBJECTIVE: To compare outcomes of in vitro fertilization (IVF) cycles with adequate versus inadequate response to the gonadotropin-releasing hormone (GnRH) agonist trigger rescued with the use of human chorionic gonadotropin (hCG) retrigger, and to identify risk factors associated with an inadequate trigger. DESIGN: Retrospective cohort study. SETTING: Private practice. PATIENT(S): Women at high risk for ovarian hyperstimulation syndrome who underwent an autologous IVF cycle and used GnRH agonist to trigger oocyte maturation before oocyte retrieval. INTERVENTION(S): Patients were triggered with GnRH agonist for final oocyte maturation before retrieval. Patients with an inadequate response, defined by low post-trigger serum LH and P concentrations or failure to recover oocytes after aspiration of several follicles, were retriggered with hCG. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, fertilization rate, clinical pregnancy, and live birth. RESULT(S): Two percent of patients triggered with GnRH agonist had an inadequate response and were retriggered with hCG. There was no statistically significant difference in clinical outcomes between the cycles that were retriggered with hCG and successful GnRH agonist triggers. Low body mass index, low baseline LH, and higher total dosage of gonadotropins required for stimulation were associated with an increased risk of having an inadequate response to the GnRH agonist trigger. CONCLUSION(S): A small minority of patients triggered with GnRH agonist had an inadequate response. Rescheduling of oocyte retrieval after hCG retrigger yielded similar IVF outcomes. Evaluation of trigger response based on serum LH and P concentrations is time dependent. Patient characteristics suggestive of hypothalamic hypofunction were predictive of an inadequate response to the GnRH agonist trigger.

Factors associated with birth outcomes from cryopreserved blastocysts: experience from 4,597 autologous transfers of 7,597 cryopreserved blastocysts.

OBJECTIVE: To evaluate factors associated with cryopreserved blastocyst transfer birth outcomes, including age, expansion time, cryopreservation protocol, cryodamage, and number of embryos transferred. DESIGN: Retrospective cohort study. SETTING: Private infertility practice. PATIENT(S): Cryopreserved blastocyst transfer patients from January 2003 to April 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Birth per transfer and children per embryo. RESULT(S): Overall live birth per transfer was 32%, with 17% twin births and 0.3% triplets. Live birth per transfer was significantly higher for vitrification compared with slow-freeze (day 5 cryopreservation: 47% vs. 35%; day 6 cryopreservation: 46% vs. 24%), as was live born children per transferred embryo (39% vs. 29% for day 5; 36% vs. 18% for day 6). Birth rates declined only slightly with increasing age at cryopreservation through 37 years, followed by an increasingly rapid decline in success with increasing age thereafter. Live birth rates declined rapidly (49%-18% for vitrification and 37%-10% for slow-freeze) as the percentage of intact cells after cryopreservation decreased from 95%-100% to 70%-79%, with almost no births when the percentage of intact cells was <70%. Increasing numbers of embryos per transfer were associated with significant increase in live birth per transfer but significant decrease in children per transferred embryo. Birth rates were much lower for blastocysts with delayed expansion on day 7 (10% per transfer). CONCLUSION(S): Birth outcomes from cryopreserved blastocyst transfer are influenced by age, timing of expansion, cryopreservation protocol, visible cryodamage, and the number of embryos transferred. Vitrification substantially improves outcomes versus slow freezing.

Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval.

OBJECTIVE: To evaluate a single treatment center's experience with autologous IVF using vitrified and warmed oocytes, including fertilization, embryonic development, pregnancy, and birth outcomes, and to estimate the likelihood of live birth of at least one, two, or three children according to the number of mature oocytes cryopreserved by elective fertility preservation patients. DESIGN: Retrospective cohort study. SETTING: Private practice clinic. PATIENT(S): Women undergoing autologous IVF treatment using vitrified and warmed oocytes. Indications for oocyte vitrification included elective fertility preservation, desire to limit the number of oocytes inseminated and embryos created, and lack of available sperm on the day of oocyte retrieval. INTERVENTION(S): Oocyte vitrification, warming, and subsequent IVF treatment. MAIN OUTCOME MEASURE(S): Post-warming survival, fertilization, implantation, clinical pregnancy, and live birth rates. RESULT(S): A total of 1,283 vitrified oocytes were warmed for 128 autologous IVF treatment cycles. Postthaw survival, fertilization, implantation, and birth rates were all comparable for the different oocyte cryopreservation indications; fertilization rates were also comparable to fresh autologous intracytoplasmic sperm injection cycles (70% vs. 72%). Implantation rates per embryo transferred (43% vs. 35%) and clinical pregnancy rates per transfer (57% vs. 44%) were significantly higher with vitrified-warmed compared with fresh oocytes. However, there was no statistically significant difference in live birth/ongoing pregnancy (39% vs. 35%). The overall vitrified-warmed oocyte to live born child efficiency was 6.4%. CONCLUSION(S): Treatment outcomes using autologous oocyte vitrification and warming are as good as cycles using fresh oocytes. These results are especially reassuring for infertile patients who must cryopreserve oocytes owing to unavailability of sperm or who wish to limit the number of oocytes inseminated. Age-associated estimates of oocyte to live-born child efficiencies are particularly useful in providing more explicit expectations regarding potential births for elective oocyte cryopreservation.

Are good patient and embryo characteristics protective against the negative effect of elevated progesterone level on the day of oocyte maturation?

OBJECTIVE: To evaluate if an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration is associated with a decrease in live-birth rate in patients with a good prognosis. DESIGN: Retrospective cohort study. SETTING: Large, private, assisted reproductive technology (ART) practice. PATIENT(S): One thousand six hundred twenty fresh autologous ART cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live-birth rate. RESULT(S): A total of 934 blastocyst and 686 cleavage-stage embryo transfer (ET) cycles were evaluated. Serum P levels were not associated with markers of oocyte or embryo quality, including fertilization, embryo stage at transfer, and embryos available for cryopreservation. Patient age, stage of ET, embryo quality, the number of embryos transferred, and P level on the day of hCG administration were all significantly associated with live birth. Higher P levels were associated with decreased odds of live birth for cleavage- and blastocyst-stage embryos, poor-fair and good-quality embryos, and poor- and high-responder patients. The nonsignificance of interaction tests of P levels with embryo stage, embryo quality, patient age, and ovarian response indicated that the relationship between P level and live birth was similar regardless of these factors. CONCLUSION(S): An elevated serum P level on the day of hCG administration was negatively associated with live birth, even in ETs with a good prognosis.

Single vitrified blastocyst transfer maximizes liveborn children per embryo while minimizing preterm birth.

OBJECTIVE: To compare live-birth rates, blastocyst to live-birth efficiency, gestational age, and birth weights in a large cohort of patients undergoing single versus double thawed blastocyst transfer. DESIGN: Retrospective cohort study. SETTING: Assisted reproduction technology (ART) practice. PATIENT(S): All autologous frozen blastocyst transfers (FBT) of one or two vitrified-warmed blastocysts from January 2009 through April 2012. INTERVENTION(S): Single or double FBT. MAIN OUTCOME MEASURE(S): Live birth, blastocyst to live-birth efficiency, preterm birth, low birth weight. RESULT(S): Only supernumerary blastocysts with good morphology (grade BB or better) were vitrified, and 1,696 FBTs were analyzed. No differences were observed in patient age, rate of embryo progression, or postthaw blastomere survival. Double FBT yielded a higher live birth per transfer, but 33% of births from double FBT were twins versus only 0.6% of single FBT. Double FBT was associated with statistically significant increases in preterm birth and low birth weight, the latter of which was statistically significant even when the analysis was limited to singletons. Of the blastocysts transferred via single FBT, 38% resulted in a liveborn child versus only 34% with double FBT. This suggests that two single FBTs would result in more liveborn children with significantly fewer preterm births when compared with double FBT. CONCLUSION(S): Single FBT greatly decreased multiple and preterm birth risk while providing excellent live-birth rates. Patients should be counseled that a greater overall number of live born children per couple can be expected when thawed blastocysts are transferred one at a time.

Single-donor and double-donor sperm intrauterine insemination cycles: does double intrauterine insemination increase clinical pregnancy rates?

OBJECTIVE: To compare the pregnancy outcomes in the setting of a single- vs. double-donor sperm intrauterine insemination (IUI) treatment cycle. DESIGN: Retrospective cohort study. SETTING: Large, private assisted reproductive technology practice. PATIENT(S): Donor sperm IUI recipients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): There were 2,486 double and 673 single-donor sperm IUI cycles. The two groups were similar for age, body mass index, and the number of prior cycles. The clinical pregnancy rates were similar between the two groups (single: 16.4% vs. double: 13.6%). In univariate regression analysis, age, total motile sperm, and diminished ovarian reserve (DOR) were associated with pregnancy. Generalized estimating equation models accounting for repeated measures, age, DOR and total motile sperm and the interactions of these factors demonstrated that single and double IUI had similar odds of pregnancy (odds ratio 1.12; 95% confidence interval, 0.96-1.44). Pregnancy rates remained similar between the two groups in matched comparison and other subgroup analyses. CONCLUSION(S): Single and double-donor IUI cycles had similar clinical pregnancy rates. This large data set did not demonstrate a benefit to routine double IUI in donor sperm cycles.

Ovarian reserve and subsequent assisted reproduction outcomes after methotrexate therapy for ectopic pregnancy or pregnancy of unknown location.

OBJECTIVE: To assess ovarian reserve after methotrexate treatment for ectopic pregnancy or pregnancy of unknown location after assisted reproductive technology (ART). DESIGN: Retrospective cohort study. SETTING: Large ART practice. PATIENT(S): Women receiving methotrexate or surgery after ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follicle-stimulating hormone (FSH), antral follicle count (AFC), and oocyte yield compared between women treated with methotrexate or surgery, with secondary outcomes of clinical pregnancy and live birth. RESULT(S): There were 153 patients in the methotrexate group and 36 patients in the surgery group. Neither group demonstrated differences in ovarian reserve or oocyte yield in a comparison of the before and after treatment values. The change in ovarian reserve and oocyte yield after treatment were similar between the two groups. The number of doses of methotrexate was not correlated with changes in ovarian reserve, indicating no dose-dependent effect. Time between treatment and repeat ART was not correlated with outcomes. Live birth in subsequent cycles was similar in the two groups. CONCLUSION(S): Ovarian reserve and subsequent ART cycle outcomes were reassuring after methotrexate or surgical management of ectopic pregnancy. No adverse impact of methotrexate was detected in this large fertility cohort as has been previously described elsewhere.