Eric Widra

The clinical relevance of luteal phase deficiency: A committee opinion

Luteal phase deficiency (LPD) has been described in healthy normally menstruating women and in association with other medical conditions. While progesterone is important for the process of implantation and early embryonic development, LPD, as an independent entity causing infertility, has not been proven.

Subclinical elevations of thyroid-stimulating hormone and assisted reproductive technology outcomes.

The prevalence of moderately elevated TSH levels consistent with subclinical hypothyroidism (2.5-4.0 μIU/mL) was 23% in a cohort of 1,231 women pursuing assisted reproductive technologies. Preconception elevated levels of TSH were associated with diminished ovarian reserve but were not associated with adverse assisted reproductive technology or pregnancy outcomes.

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.

Uterine septum: a guideline

The purpose of this guideline is to review the literature regarding septate uterus and determine optimal indications and methods of treatment for it. Septate uterus has been associated with an increase in the risk of miscarriage, premature delivery, and malpresentation; however, there is insufficient evidence that a uterine septum is associated with infertility. Several studies indicate that treating a uterine septum is associated with an improvement in live-birth rates in women with a history of prior pregnancy loss, recurrent pregnancy loss, or infertility. In a patient without infertility or prior pregnancy loss, it may be reasonable to consider septum incision following counseling regarding potential risks and benefits of the procedure. Many techniques are available to surgically treat a uterine septum, but there is insufficient evidence to recommend one specific method over another.

Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline

Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to identify who is at high risk, how to prevent OHSS, and the treatment for existing OHSS.

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 womans 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 prediction model for live birth and multiple births within the first three cycles of assisted reproductive technology.

OBJECTIVE To develop a model predictive of live-birth rates (LBR) and multiple birth rates (MBR) for an individual considering assisted reproduction technology (ART) using linked cycles from Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) for 2004-2011. DESIGN Longitudinal cohort. SETTING Clinic-based data. PATIENT(S) 288,161 women with an initial autologous cycle, of whom 89,855 did not become pregnant and had a second autologous cycle and 39,334 did not become pregnant in the first and second cycles and had a third autologous cycle, with an additional 33,598 women who had a cycle using donor oocytes (first donor cycle). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) LBRs and MBRs modeled by womans age, body mass index, gravidity, prior full-term births, infertility diagnoses by oocyte source, fresh embryos transferred, and cycle, using backward-stepping logistic regression with results presented as adjusted odds ratios (AORs) and 95% confidence intervals. RESULT(S) The LBRs increased in all models with prior full-term births, number of embryos transferred; in autologous cycles also with gravidity, diagnoses of male factor, and ovulation disorders; and in donor cycles also with the diagnosis of diminished ovarian reserve. The MBR increased in all models with number of embryos transferred and in donor cycles also with prior full-term births. For both autologous and donor cycles, transferring two versus one embryo greatly increased the probability of a multiple birth (AOR 27.25 and 38.90, respectively). CONCLUSION(S) This validated predictive model will be implemented on the Society for Assisted Reproductive Technology Web site (www.sart.org) so that patients considering initiating a course of ART can input their data on the Web site to generate their expected outcomes.

The use of preimplantation genetic testing for aneuploidy (PGT-A): a committee opinion

The value of preimplantation genetic testing for aneuploidy (PGT-A) as a screening test for in vitro fertilization (IVF) patients has yet to be determined. Several studies demonstrate higher birth rates after aneuploidy testing and elective single-embryo transfer (eSET), suggesting the potential for this testing to decrease the risk of multiple gestations, though these studies have important limitations.

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.

Combined hormonal contraception and the risk of venous thromboembolism: a guideline

While venous thromboembolism (VTE) is rare in young women of reproductive age, combined oral contraceptives increase the risk of VTE. In the patient in whom combined hormonal contraception is appropriate, it is reasonable to use any currently available preparation.