K. Devine

Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.

OBJECTIVE To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. DESIGN Decision-tree mathematical model with sensitivity analyses. SETTING Not applicable. PATIENT(S) A simulated cohort of women wishing to delay childbearing until age 40 years. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) Cost per live birth. RESULT(S) Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from

Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles

55,060 to

Diminished ovarian reserve in the United States assisted reproductive technology population: diagnostic trends among 181,536 cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System

39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to

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

61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. CONCLUSION(S) In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

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

OBJECTIVE To compare the effect of progesterone (P) on the day of trigger in fresh assisted reproduction technology (ART) transfer cycles versus its effect on subsequent frozen embryo transfer (FET) cycles. DESIGN Retrospective cohort study. SETTING Large private ART practice. PATIENT(S) Fresh autologous and FET cycles from 2011-2013. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Live birth. RESULT(S) A paired analysis of patients who underwent both a fresh transfer and subsequent FET cycle and an unpaired analysis of data from all fresh transfer cycles and all FET cycles were performed. We analyzed 1,216 paired and 4,124 unpaired cycles, and P was negatively associated with birth in fresh but not FET cycles in all analyses. Interaction testing of P and cycle type indicated P had a different association with birth in fresh versus FET cycles. When P was ≥ 2 ng/mL at the time of trigger, live birth was more likely in FET versus fresh cycles in the paired analysis (47% vs. 10%), in the unpaired analysis (51% vs. 14%), and in unpaired, good blastocyst only transfer subgroup (51% vs. 29%). Live birth was similar in FET cycles, with P ≥ 2 ng/mL versus P < 2 ng/mL (51% vs. 49%). Conversely, live birth was lower in fresh cycles, with P ≥ 2 ng/mL versus P <2 ng/mL (15% vs. 45%). CONCLUSION(S) Elevated P levels on the day of trigger during the initial fresh cycle were negatively associated with live birth in the fresh transfer cycles but not in subsequent FET cycles. Freezing embryos and performing a subsequent FET cycle ameliorates the effect of elevated P on live-birth rates.

The Affordable Care Act: early implications for fertility medicine.

OBJECTIVE To evaluate trends in diminished ovarian reserve (DOR) assignment in the Society for Assisted Reproductive Technology (SART) Clinic Outcomes Reporting System database and to evaluate its accuracy in predicting poor ovarian response (POR) as defined in European Society of Human Reproduction and Embryologys Bologna criteria (2011). DESIGN Retrospective cohort study. SETTING Not applicable. PATIENT(S) A total of 181,536 fresh, autologous ART cycles reported to SART by U.S. clinics in 2004 and 2011 (earliest and most recent available reporting years). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) DOR assignment was the primary exposure. POR, defined as cycle cancellation for poor response or less than 4 oocytes retrieved after conventional gonadotropin stimulation (>149 IU FSH daily), was the primary outcome. Secondary outcomes were live birth and number of oocytes retrieved. DOR prevalence, power of DOR and FSH (</≥12 mIU/mL) to predict POR, and live birth in POR cycles were also calculated. RESULT(S) DOR prevalence increased from 19% to 26% from 2004 to 2011. Among cycles clinically assigned as DOR, incidence of POR decreased from 32% to 30%, and live birth improved from 15% to 17%. Comparing basal FSH ≥12 versus clinical assignment of DOR, basal FSH had a higher specificity (92.2% vs. 81.6%) and positive predictive value (38.3% vs. 30.9%) for predicting POR. Live birth among POR cycles was 4%. CONCLUSION(S) DOR diagnosis is increasing, and accuracy remains poor, despite the availability of additional diagnostic parameters such as antral follicle count and antimüllerian hormone. POR entailed poor outcomes, but the majority of patients clinically assigned as DOR did not experience POR. Development and use of more accurate predictors of POR are needed to minimize patient distress resulting from overdiagnosis.

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

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 INTEREST(S) No external funding was received for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.

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

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.

Is Magnetic Resonance Imaging Sufficient to Diagnose Rudimentary Uterine Horn? A Case Report and Review of the Literature

With the majority of the law taking effect in 2014, insurers, patients, and healthcare providers in every field of medicine anxiously await the full impact of the Patient Protection and Affordable Care Act (ACA). Patients with infertility and the field of Fertility Medicine stand much to gain, given that so few patients enjoy substantial coverage for fertility treatments. Conversely, given the ACA’s basis of ‘minimum essential’ coverage, our patients’ and the field’s position is precarious -- fertility treatments have historically been regarded as a luxury by insurers – and what little coverage exists may be further downscaled. Approximately 10% of American couples experience infertility, defined as no pregnancy over 12 months of sexual activity without contraception. Of those who seek infertility evaluation, about half undergo fertility treatment, and the likelihood of proceeding with therapy is associated with healthcare coverage status. Yet the vast majority of Americans lack healthcare coverage for infertility treatments. A quarter of U.S. health insurance plans include some infertility benefit, and at present, 15 states mandate that group insurers offer some infertility benefit to employers. Two of these states, California and Texas, mandate only that group insurers offer infertility coverage -- employers are not obligated to provide it to their employees. A handful of these 15 apply the mandate to both group and individual insurers, the latter of which sell policies directly to the insured, rather than to their employer. The mandated procedures in some states are diagnostic rather than therapeutic. Only 7 states (Arkansas, Connecticut, Hawaii, Illinois, Maryland, Massachusetts, and New Jersey) specifically require that employers cover any IVF. Of these, Arkansas requires only

Does premature elevated progesterone on the day of trigger increase spontaneous abortion rates in fresh and subsequent frozen embryo transfers

15,000 coverage, and Hawaii requires coverage for only one IVF cycle. Among other substantial restrictions and exclusions, small employers and religiously-affiliated employers are generally exempt from the requirement. The end result is that even in so-called ‘mandated states,’ patients may pay for most, if not all of the treatment for their infertility, particularly when ART is needed. That said, in states where insurers have been mandated to cover infertility treatment, utilization of fertility medical care is significantly increased. With implementation of the ACA, the market for health insurance in the United States is poised for dramatic change. Long term repercussions of the law on insurance markets may serve either to further diminish or to expand coverage for fertility care. Here we review the early indications of the ACA’s effects on fertility medicine.