Endometrial preparation before the transfer of single, vitrified-warmed, euploid blastocysts: does the duration of estradiol treatment influence clinical outcome?

OBJECTIVE: To investigate whether the duration of estrogen administration before euploid embryo transfer affects clinical outcome. DESIGN: Retrospective cohort study. SETTING: Private, academic fertility center. PATIENT(S): Patients (n = 1,439) undergoing autologous freeze-only in vitro fertilization with preimplantation genetic testing (PGT) followed by endometrial preparation with estrogen and progesterone in a frozen, euploid blastocyst transfer cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome was live birth, and secondary outcomes included implantation, clinical pregnancy, early pregnancy loss, live birth, infant birthweight, low birth weight, infant gestational age at delivery, and preterm birth. RESULT(S): The duration of estrogen administration (mean: 17.5 ± 2.9 days; range: 10-36 days) before frozen embryo transfer did not impact implantation (odds ratio [OR] 0.99; 95% confidence interval [CI], 0.95-1.03), clinical pregnancy (OR 0.98; 95% CI, 0.94-1.01), early pregnancy loss (OR 1.03; 95% CI, 0.95-1.12), or live birth (OR 0.99; 95% CI, 0.95-1.03). The duration of estrogen exposure did not affect infant birthweight (in grams) (ß= -10.65 ± 8.91) or the odds of low birth weight (OR 0.87; 95% CI, 0.68-1.13). For every additional day of estrogen administration, we observed a reduction in gestational age at delivery (in weeks) (ß= -0.07 ± 0.03), but the odds of preterm delivery were not affected (OR 1.05; 95% CI, 0.95-1.17). CONCLUSION(S): Variation in the duration of estradiol supplementation before progesterone initiation does not impact frozen, euploid blastocyst transfer outcome. The duration of estrogen administration was inversely correlated with gestational age at delivery, but this did not translate into an increase in preterm delivery. Further studies are required on the downstream effects of endometrial preparation on the placental-endometrium interface.

The correlation between morphology and implantation of euploid human blastocysts.

RESEARCH QUESTION: Does the composite morphology score or a particular developmental component (expansion stage, inner cell mass [ICM] or trophectoderm [TE]) of euploid blastocysts undergoing single frozen embryo transfer (FET) impact ongoing pregnancy/live birth (OP/LB) rates? DESIGN: Retrospective cohort study including a total of 2236 embryos from 1629 patients who underwent single euploid FET between 2012 and 2017. RESULTS: Embryos with an ICM grade of A compared with C had a higher OP/LB rate (55.6% versus 32.3%, P < 0.001). Blastocysts with a TE grade of A or B compared with C had a higher likelihood of OP/LB (A versus C: odds ratio [OR] 1.6, 99% confidence interval [CI] 1.1-2.3, B versus C: OR 1.5, 99% CI 1.1-2.1), and blastocysts with a developmental stage of 4 or 5 compared with 6 had higher odds of OP/LB (4 versus 6: OR 1.6, 99% CI 1.2-2.2, 5 versus 6: OR 1.6, 99% CI 1.2-2.3). CONCLUSIONS: Among euploid embryos, ICM morphology is the best predictor of sustained implantation; however, a composite score may provide additional guidance. While there is a known benefit in genomic screening prior to embryo selection, morphology provides individualized, prognostic information about implantation potential.

Insulin Resistance and ß-cell Function Calculated by Homeostasis Model Assessment in Lean, Overweight, and Obese Women with Polycystic Ovary Syndrome.

OBJECTIVE: To evaluate the homeostasis model assessment (HOMA) measurement of insulin resistance (IR) and pancreatic ß-cell function (%ß) and compare those values between groups of healthy-weight, over-weight, and obese women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Retrospective cohort study of women aged 24-48 with PCOS, diagnosed according to 2004 Rotterdam criteria. Participants were grouped by BMI. Quantitative variables were compared by one-way ANOVA and the Tukey method. Analysis for power to detect a difference between means was conducted. Pearson correlation was used to test differences in frequency distribution. RESULTS: By BMI category, 29 participants were of healthy weight, 11 were overweight, and 11 were obese. HOMA-IR was significantly higher in obese women as compared to overweight and healthy-weight patients (2.88 ± 2.09, 1.13 ± 0.73, 0.84 ± 0.49, respectively; p <0.0001). Moreover, HOMA-%ß was significantly increased in obese women as compared to overweight and healthy-weight patients (186.89 ± 131.62, 106.83 ± 46.77, 86.60 ± 40.91, respectively; p<0.0001). Adequate statistical power was not present to distinguish a difference between overweight and normal-weight participants. A positive linear correlation was found between log HOMA-IR and BMI, and between log HOMA-%ß and BMI. CONCLUSION: Obese PCOS patients have a higher risk of elevated insulin resistance and ß-cell function than do those with BMI <30.

Positive Chlamydia trachomatis serology result in women seeking care for infertility is a negative prognosticator for intrauterine pregnancy.

BACKGROUND: There are no prior studies that assess the non-in vitro fertilization (IVF) pregnancy rates in chlamydia serology-positive versus serology-negative women. Therefore, we wanted to determine whether a positive Chlamydia trachomatis immunoglobulin G serology result predicts reduced clinical pregnancy rates without IVF. METHODS: A prospective observational study was performed at a university-affiliated reproductive center. A total of 1279 new infertility patients seen at the Continuum Reproductive Center between January 2007 and June 2009 underwent C. trachomatis immunoglobulin G screening. Charts were later reviewed for hysterosalpingography, laparoscopy, treatment cycles, and ultrasound evidence of an intrauterine pregnancy. The main outcome measure was non-IVF cumulative pregnancy rates. RESULTS: Seventy (5.5%) of 1279 of the participants were found to have a positive chlamydia serology result. Serology-positive participants had significantly more tubal block on hysterosalpingography (37.5% vs. 10.1%, P = 0.001) and laparoscopically confirmed tubal damage (85.7% vs. 48.9%, P = 0.002). The percent of all participants who achieved an ultrasound documented clinical pregnancy, at our center, without IVF was significantly lower among Chlamydia-positive participants (10.0% versus 21.7%) in seronegative participants (P < 0.02). The hazard rate of non-IVF clinical pregnancy among chlamydia antibody testing-positive patients was 57% less than the rate of pregnancy among chlamydia antibody testing-negative patients (hazard ratio, 0.43; 95% confidence interval, 0.20-0.92). Both the per-cycle and the cumulative IVF pregnancy rates were equivalent in seropositive and in seronegative participants. CONCLUSIONS: This is the first large study to report that a positive serology screening result is both predictive of tubal damage and a reduced cumulative pregnancy rate when excluding treatment with IVF.

Elevated progesterone-to-estradiol ratio versus serum progesterone alone for predicting poor cycle outcome with in vitro fertilization.

OBJECTIVE: To determine whether a progesterone-to-estradiol (P/E2) ratio on day of human chorionic gonadotropin (hCG) administration would be a better predictor of in vitro fertilization (IVF) outcome than serum P alone. STUDY DESIGN: All 348 fresh IVF cycles performed in 2002 and 2003 at a university hospital center were reviewed for all cycle parameters as related to the peak P and peak P/E2 ration on day hCG administration. RESULTS: Out of the 348 cycles performed, 199 cycles resulted in clinical pregnancies. The mean P level (1.4 ng/mL) was equivalent in both conception and nonconception cycles. A P/E2 ratio > 1.0, however, was associated with a highly significant reduction in clinical pregnancy rate (38.2% vs. 62.6%, p< 0.01) and live birth rate (35.4% vs. 49.1%, p = 0.02). CONCLUSION: Cycles with elevated P/E2 ratios are associated with lower clinical pregnancy and live birth rates, which decrease further as the P/E2 ratio rises. P/E2 ratio improves the prediction of IVF outcome when compared to serum P levels alone.

Hysterosalpingography versus sonohysterography for intrauterine abnormalities.

OBJECTIVE: The hysterosalpingogram is commonly used to evaluate the uterine cavity and the fallopian tubes in the workup of infertile couples. The sonohysterogram is gaining popularity as part of this evaluation. This study compares hysterosalpingography to sonohysterography for the detection of polyps, cavitary fibroids, adhesions, and septae in infertile patients. METHODS: We conducted a retrospective chart review of 149 infertility patients seen at a University Hospital Center, divisions of Reproductive Endocrinology and Interventional Radiology. Patients underwent hysterosalpingography and sonohysterography as part of their infertility evaluation. The reports were reviewed and findings like polyps, fibroids, adhesions, and septae were compared to the findings obtained at the time of hysteroscopy. Sensitivity, specificity, and accuracy of radiologic tests were the main outcome measures. RESULTS: The sensitivity of hysterosalpingography and sonohysterography was 58.2% and 81.8%, respectively. The specificity for hysterosalpingography and sonohysterography was 25.6% and 93.8%. The differences in sensitivity and specificity were both statistically significant. Hysterosalpingography had a general accuracy of 50.3%, while sonohysterography had a significantly higher accuracy of 75.5%. CONCLUSION: Although hysterosalpingography is the standard screening test for the diagnosis of tubal infertility and can provide useful information about the uterine cavity, sonohysterography is more sensitive, specific, and accurate in the evaluation of the uterine cavity.

A comparison of gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist flare protocols for poor responders undergoing in vitro fertilization.

OBJECTIVE: To compare stimulation profiles, pregnancy, and live birth rates in poor responders during in vitro fertilization (IVF) cycles using either a gonadotropin-releasing hormone (GnRH) antagonist (cetrorelix) or a GnRH agonist flare protocol (leuprolide). DESIGN: Retrospective chart review. SETTING: A university-affiliated IVF program. PATIENT(S): Women designated as poor responders based on a prior stimulation cycle or baseline follicle-stimulating hormone (FSH) level of >10 mIU/mL, who needed at least 375 IU of starting daily gonadotropins in the study cycle. INTERVENTION(S): Administration of GnRH agonist flare or GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate. RESULT(S): For 68 GnRH antagonist and 45 GnRH agonist flare cycles, the groups were similar with respect to age (38.8 versus 38.6 years) and basal FSH concentration (8.33 versus 8.65 mIU/mL). No statistically significant differences between the protocol types were noted in peak estradiol levels, amount of gonadotropins used, number of oocytes obtained, or embryos transferred. The pregnancy rates (40% versus 45.2%) and live birth rates (27.7% versus 31.7%) in the GnRH antagonist and flare groups, respectively, were similar. CONCLUSION(S): We achieved excellent and comparable pregnancy and live birth rates in poor responders of advanced reproductive age with the use of either GnRH antagonist or flare protocol.

Comparison of FSH flare with and without pretreatment with oral contraceptive pills in poor responders undergoing in vitro fertilization.

OBJECTIVE: To compare FSH, LH, estrogen, and P flare response following 1 mg lupron injection in poor responders with or without pretreatment with oral contraceptive pills (OCPs). DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Poor responders undergoing IVF flare protocol from October 2002 to November 2003. INTERVENTION(S): Patients were divided into group A, who received OCPs before IVF cycle (n = 12), and group B, who did not (n = 7). One milligram Lupron was injected SC after measuring day 2 serum FSH, LH, estrogen, and P. After 24 hours, serum hormones were measured before lupron administration. MAIN OUTCOME MEASURE(S): Serum FSH, LH, estrogen, and P before and after 1 mg lupron RESULT(S): Basal FSH was similar in both groups (8.6 +/- 4.5 vs. 9.6 +/- 2.9 mIU/mL). Group A patients had significantly lower day 2 FSH (3.6 +/- 3.6 vs. 10.1 +/- 4.2 mIU/mL; P<.05). After lupron, although both groups had a significant rise in FSH and LH, mean LH rise in group B was 39.5 +/- 31 mIU/mL versus 11.3 +/- 4.6 mIU/mL in group A (P<.05). CONCLUSION(S): Pretreatment with OCPs in GnRH agonist flare protocol suppresses pre-Lupron FSH but does not blunt FSH flare. It blunts LH flare, which may be beneficial.

Successful pregnancy rates achieved with day 4 embryo transfers.

OBJECTIVE: To assess the success of day 4 embryo transfers (ETs) following IVF at one institution. DESIGN: Retrospective analysis. SETTING: A university hospital IVF program. PATIENT(S): Two hundred nondonor, fresh IVF cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE: Outcomes of IVF. Outcome assessments after day 4 ETs included rates of implantation, clinical pregnancy, and singleton and multiple live births. RESULT(S): The overall live-birth rate was 54.4%. Implantation rates were highest in younger age groups, and similar in patients 35-40 years of age. Pregnancy and live-birth rates were similar across all age groups up to age 40 years. Multiple gestations were highest in women < or =40 years of age. CONCLUSION: Acceptable pregnancy rates can be achieved with day 4 ETs.