Mitigating multiples, less is more: examining trends in multifetal gestation rates with assisted reproductive technology.

PURPOSE: Multifetal gestation (MFG) is much more common in pregnancies that utilize assisted reproductive technologies (ART). We assessed how these rates have changed over the previous decade and the impact on live birth rates (LBR). METHODS: This retrospective cohort study uses the National Summary Reports of the Society for Assisted Reproductive Technology (SART) from 2014 to 2020. Data points included only autologous cycles. The data were divided into five age groups as reported in the database: < 35, 35-37, 38-40, 41-42, and > 42 years old. Descriptive statistics and a two-tailed T-test were used to determine the trends and statistical significance (p < 0.05). RESULTS: Rates of twin births decreased substantially from 2014 to 2020 for autologous embryo transfers across all age groups and diagnoses. Surprisingly, the overall LBR for autologous IVF cycles decreased at similar rates from 2014 to 2020 in all age groups. The mean number of embryos transferred has dramatically reduced, especially across age groups < 42. CONCLUSION: Rates of twin and higher-level gestations have decreased substantially over the past decade; the effect correlates with the increased utilization of eSET and PGT. The cause of infertility did not significantly impact the rate of MFG.

Comparing blastocyst quality and live birth rates of intravaginal culture using INVOcell™ to traditional in vitro incubation in a randomized open-label prospective controlled trial.

PURPOSE: The purpose of this study is to to compare the efficacy of intravaginal culture (IVC) of embryos in INVOcell™ (INVO Bioscience, MA, USA) to traditional in vitro fertilization (IVF) incubators in a laboratory setting using a mild pre-determined stimulation regimen based solely on anti-mullerian hormone (AMH) and body weight with minimal ultrasound monitoring. The primary endpoint examined was total quality blastocysts expressed as a percentage of total oocytes placed in incubation. Secondary endpoints included percentage of quality blastocysts transferred, pregnancy, and live birth rates. METHODS: In this prospective randomized open-label controlled single-center study, 40 women aged <38 years of age with a body mass index (BMI) of <36 and an AMH of 1-3 ng/mL were randomized prior to trigger to receive either IVC or IVF. Controlled ovarian stimulation was administered with human menopausal gonadotropin (hMG) in a fixed gonadotropin-releasing hormone (GnRH) agonist cycle based solely on AMH and body weight. A single ultrasound-monitoring visit was performed on the 10th day of stimulation. One or two embryos were transferred following 5 days of culture. RESULTS: IVF produced a greater percentage of total quality embryos as compared to IVC (50.6 vs. 30.7 %, p = 0.0007, respectively). There was no significant difference between in IVF and IVC in the percentage of quality blastocysts transferred (97.5 vs. 84.9 %, p = 0.09) or live birth rate (60 % IVF, 55 % IVC). CONCLUSIONS: IVF was shown to be superior to IVC in creating quality blastocysts. However, both IVF and IVC produced identical blastocysts for transfer resulting in similar live birth rates. IVC using INVOcell™ is effective and may broaden access to fertility care in selected patient populations by ameliorating the need for a traditional IVF laboratory setting. Further studies will help elucidate the potential physiological, psychological, geographic, and financial impact of IVC on the delivery of fertility care.

Predictive value of postwashed total progressively motile sperm count using CASA estimates in 6871 non-donor intrauterine insemination cycles.

PURPOSE: To determine whether postwashed total progressively motile sperm count (TPMSC) obtained by CASA estimates could predict positive pregnancy test result in non-donor IUI cycles. METHODS: Six thousand eight hundred and seventy one (6,871) IUI cycles with non-donor semen were retrospectively analyzed. Patient, cycle characteristics and prewashed and postwashed semen parameters were included in analysis. The main outcome measure was the positive pregnancy test result. RESULTS: The pregnancy rate per cycle (PR/cycle) when postwashed TPMSC is between 0-0.5 million, 0.51-1 million, 1.01-5 million, 5.01-10 million and greater than 10 million were 8.1% (42/520), 14.4 % (41/285), 16.1% (237/1,469), 18.4% (193/1,046) and 18.8% (668/3,551) respectively. The predicted odd of positive pregnancy result is statistically significantly higher when TPMSC is >0.51 million compared to the TPMSC of <0.51 million (OR = 1.68, 95% CI: 1.04-2.71). The predicted odd of positive pregnancy result is greatest when TPMSC is at least 5 million (OR = 2, 95% CI: 1.38 to 2.9). CONCLUSION: TPMSC is an independent predictor of pregnancy test result and TPMSC of half million or greater is adequate to achieve statistically similar pregnancy test results after non-donor IUI cycles.

Use of recombinant human chorionic gonadotropin in ovulation induction.

To review the use of hCG and to describe the clinical benefit of recombinant hCG (r-hCG) based on the published results of prospective, randomized studies. Review of published articles. Tertiary infertility care center.None.None. Oocyte number and quality, luteal phase progesterone, pregnancy and OHSS rate, and local tolerability. The published data consistently show that single doses of 250 microg r-hCG and 5,000 IU urinary (u)-hCG produce similar clinical outcomes when used in infertility treatment cycles for timed intercourse, IUI, and IVF in terms of the number of oocytes retrieved, number of mature oocytes harvested, and fertilization and pregnancy rates attained. Single doses of 10,000 IU u-hCG also gave results comparable to single doses of 250 microg r-hCG. P levels in the midluteal phase were significantly higher with the use of r-hCG compared with u-hCG, and local injection site adverse effects were significantly less frequent, demonstrating the higher purity of the recombinant product. A single 500-microg dose of r-hCG led to a higher rate of ovarian hyperstimulation syndrome compared with a 250-microg dose, with no significant improvement in pregnancy rates.A single dose of 250 microg r-hCG was at least as effective as single doses of 5,000 or 10,000 IU u-hCG but offered the advantages associated with use of a recombinant product: local injection site adverse effects were significantly less frequent with r-hCG than with u-hCG.

Abdominal myomectomy--a safe procedure in an ambulatory setting.

OBJECTIVE: To evaluate the efficacy and safety of minilaparotomy myomectomy in an ambulatory setting. DESIGN: Retrospective, nonrandomized study. SETTING: Center for Assisted Reproduction, Bedford, Texas. PATIENT(S): One hundred eighty-nine women desiring fertility with symptomatic uterine leiomyomata. INTERVENTION(S): Minilaparotomy myomectomy in an ambulatory setting. MAIN OUTCOME MEASURE(S): Operative time, blood loss, recovery time, postoperative analgesia, and complications. RESULT(S): The mean diameter of the largest leiomyoma was 4.4 cm (range, 1-14 cm). The mean number and weight of the leiomyomata was 4.9 (range, 1-35) and 109.8 gm (range, 1-1,165 g), respectively. The mean operative time was 73 minutes, and the mean blood loss was 96 mL. On average, patients required 3.5 hours of recovery time. In the recovery room, patients received a mean of 12 mg of morphine/37 mg of meperidine for pain control postoperatively before discharge home. Only one major complication, pulmonary edema related to extubation, occurred. CONCLUSION(S): This study demonstrates that minilaparotomy myomectomy, when performed using a systematic operative technique, can be accomplished in an outpatient setting with minimal blood loss, fast recovery time, and a low complication rate. Postoperatively, patients require minimal analgesia, which permits them to be discharged home the same day. Minilaparotomy myomectomy is a safe, cost-effective treatment of most symptomatic uterine leiomyomata in an ambulatory setting.

Repetitive oocyte donation does not decrease serum anti-Müllerian hormone levels.

OBJECTIVE: To determine if the anti-Müllerian hormone (AMH), a proposed marker of ovarian aging, decreases with repetitive oocyte donation. DESIGN: Retrospective cohort. SETTING: Academic. PATIENT(S): Thirty-six young women who underwent three to seven oocyte donation cycles. INTERVENTION(S): Assessor blind determination of AMH levels from serum samples collected during each treatment cycle. MAIN OUTCOME MEASURE(S): Cycle trends of serum AMH levels. RESULT(S): The AMH was the only predictor of oocyte yield in the first cycles. The AMH was negatively associated with donor age and follicle stimulating hormone (FSH) dose used. Serum AMH levels did not show any decrease per treatment cycle basis and per maximum number of oocyte donation cycles performed per woman. Whereas donors who underwent six cycles showed increasing AMH levels when controlled for studied covariates, the slopes of the multiple regression curves were not significantly different from donors who underwent three, four, and five cycles. Clinical outcome assessed by FSH dose/number of oocytes ratio did not show significant change over repetitive cycles. Intercycle variation of AMH in all patients over three cycles was found to be 12.5%, which was within the reported intermenstrual range. CONCLUSION(S): Serum AMH levels do not decrease over repetitive oocyte donation cycles, which may imply that accelerated ovarian aging may not occur in oocyte donors.

Serum cetrorelix concentrations do not affect clinical pregnancy outcome in assisted reproduction.

OBJECTIVE: To analyze the potential association between serum cetrorelix levels and clinical pregnancy outcome in patients who had undergone assisted reproduction cycles with a GnRH antagonist cetrorelix acetate 3-mg injection. DESIGN: Retrospective case-control study. SETTING: University-affiliated private-assisted reproduction center. PATIENT(S): 130 IVF and intracytoplasmic sperm injection first cycles, treated with the same cetrorelix acetate protocol, in two matched groups according to whether the cycle resulted in clinical pregnancy (n = 56) or not (n = 74). INTERVENTION(S): Cetrorelix acetate administration at 3 mg in a sandwich protocol. MAIN OUTCOME MEASURE(S): Serum cetrorelix concentrations on the day of hCG administration with regard to clinical pregnancy outcome, pre- versus post-hCG percent change in serum E(2) levels and implantation rates. RESULT(S): The cetrorelix serum concentrations were in the range of 0.29 to 5.12 ng/mL. The comparisons between groups with and without clinical pregnancy revealed comparable serum cetrorelix levels. There was no significant correlation between the serum cetrorelix concentrations and percent change in pre- versus post-hCG serum E(2) levels. Serum cetrorelix levels were comparable among patients with various implantation rates. CONCLUSION(S): Although a wide range of serum cetrorelix levels could be detected during a GnRH antagonist cycle, these levels were comparable in patients with and without clinical pregnancies.

Late stages of embryo progression are a much better predictor of clinical pregnancy than early cleavage in intracytoplasmic sperm injection and in vitro fertilization cycles with blastocyst-stage transfer.

OBJECTIVE: To define and validate metrics of embryo progression and morphology during extended embryo culture and to compare the effects of early cleavage (EC) vs. blastulation stages on clinical pregnancy. DESIGN: Retrospective observational study. SETTING: University-affiliated assisted reproduction center. PATIENT(S): One thousand two hundred ninety-two intracytoplasmic sperm injection and 842 IVF blastocyst-transfer cycles. INTERVENTION(S): The embryo progression index (EPI) was calculated as the area under the curve of total cell number (TCN) over time, by using observed TCN for cleavage-stage embryos and estimated blastocyst TCN according to morphology. The EPI from days 1-3 measured early cleavage, and blastulation was assessed by EPI over extended embryo culture. Blastocyst morphology was converted into numerical blastocyst quality scores (BQSs). Receiver operating characteristic curve analysis was used to evaluate predictors for clinical pregnancy. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Per-cycle mean EPI and mean BQS for all embryos developing into blastocysts, as well as mean BQS of the transferred embryos, were significant predictors of clinical pregnancy in intracytoplasmic sperm injection and IVF cycles. Mean EPI for days 1-3 did not predict outcome. CONCLUSION(S): Early cleavage is a putative marker of embryo quality. Late-stage embryo development is more sensitive and specific in predicting clinical pregnancy than is early cleavage, supporting the use of extended embryo culture for embryo selection. The embryo progression index and BQS may also be used for this purpose.

Precycle administration of GnRH antagonist and microdose HCG decreases clinical pregnancy rates without affecting embryo quality and blastulation.

The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone (GnRH) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571) cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13-14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores. The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol, although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups. Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support resulted in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation parameters were comparable.