Academic Assisted Reproductive Technology Research Articles

Endometriosis and spontaneous hemoperitoneum in pregnancy: evaluation of the magnitude of the risk in women becoming pregnant via in vitro fertilization

To estimate the frequency of spontaneous hemoperitoneum in pregnancy (SHiP) in women with endometriosis achieving pregnancy with invitro fertilization (IVF). Retrospective case series. Referral academic assisted reproductive technology (ART) center. Three hundred and forty-eight women with a history of surgery for endometriosis and women with ovarian endometriomas or deep endometriotic nodules detected at basal transvaginal ultrasound performed before IVF cycle. Information obtained from patients' charts on basal characteristics, IVF cycle, and pregnancy outcomes, and binomial distribution model created to determine the 95% confidence interval (CI) of the proportion of SHiP. Rate of SHiP. Overall, 362 pregnancies were included, among which 238 (66%) had a history of previous surgery for endometriosis and 231 (64%) had endometriosis detected at ultrasound (107 women, 30%, had both). Pregnancies were achieved after fresh and frozen cycles in 244 (67%) and 118 (33%) women, respectively. One case of SHiP was recorded, corresponding to a rate of 0.3%. In the general population of women with endometriosis undergoing IVF, SHiP is uncommon. Future studies should better identify the risk factors for SHiP to disentangle the subgroups of women at higher risk.

Assessing the use of assisted reproductive technology in the United States by non–United States residents

To study cross-border reproductive care (CBRC) by assessing the frequency and nature of assisted reproductive technology (ART) care that non-U.S. residents receive in the United States. Retrospective study of ART cycles reported to the Centers for Disease Control and Prevention's National ART Surveillance System (NASS) from 2006 to2013. Private and academic ART clinics. Patients who participated in ART cycles in the United States from 2006 to2013. None. Frequency and trend of ART use in the U.S. by non-U.S. residents, countries of residence for non-U.S. residents, differences by residence status for specific ART treatments received, and the outcomes of these ART cycles. A total of 1,271,775 ART cycles were reported to NASS from 2006 to 2013. The percentage of ART cycles performed for non-U.S. residents increased from 1.2% (n = 1,683) in 2006 to 2.8% (n = 5,381) in 2013 (P<.001), with treatment delivered to residents of 147 countries. Compared with resident cycles, non-U.S. resident cycles had higher use of oocyte donation (10.6% vs. 42.6%), gestational carriers (1.6% vs. 12.4%), and preimplantation genetic diagnosis or screening (5.3% vs. 19.1%). U.S. resident and non-U.S. resident cycles had similar embryo transfer and multiple birth rates. This analysis showed that non-U.S. resident cycles accounted for a growing share of all U.S. ART cycles and made higher use of specialized treatment techniques. This study provides important baseline data on CBRC in the U.S. and may also prove to be useful to organizations interested in improving access to fertility treatments.

Reduced neurotrophin receptor tropomyosin-related kinase A expression in human granulosa cells: a novel marker of diminishing ovarian reserve

To determine whether human mural and cumulus granulosa cell neurotrophin and neurotrophin receptor content correlate to ovarian reserve markers. Prospective, laboratory-based study. Academic assisted reproductive technology (ART) program. Twenty-three women undergoing ART. Mural and cumulus granulosa cells were collected from women undergoing oocyte retrieval during ART cycles. Relative messenger RNA (mRNA) levels of neurotrophins and their receptors were measured by quantitative reverse transcription-polymerase chain reaction and correlated to serum antimüllerian hormone (AMH) levels and the number of oocytes retrieved. Number of oocytes retrieved. Mural and cumulus granulosa cell nerve growth factor receptor tropomyosin-related kinase A (TrkA) mRNA correlated strongly to the number of oocytes retrieved. Similarly, higher serum AMH was associated with higher cumulus granulosa cell TrkA mRNA. Both mural and cumulus granulosa cell p75(NTR)/TrkA ratios were lower in women with higher serum AMH, and the number of oocytes retrieved was greater among women with low p75(NTR)/TrkA ratio. No significant associations were found between brain-derived neurotrophic factor (BDNF) and its specific receptor tropomyosin-related kinase B (TrkB) and ovarian reserve markers. Although BDNF and TrkB expression were higher in cumulus compared with mural granulosa cells, no such association was found between TrkA and granulosa cells. Antimüllerian hormone and cumulus TrkA mRNA, in a model incorporating both, correlated strongly to the number of oocytes retrieved (R(2) = 0.84). Cumulus TrkA and p75(NTR) mRNA correlate to ovarian reserve, whereas BDNF and TrkB are associated with the type of granulosa cell.

A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth rate than a natural endogenous hormone protocol for frozen-thawed blastocyst-stage embryo transfer cycles: an analysis of 1391 cycles

To compare embryo and birth data in cryopreserved-thawed blastocyst-stage ET cycles between natural endogenous hormone cycles and exogenous hormone stimulation cycles. Retrospective cohort analysis. Large academic assisted reproductive technology center. One thousand three hundred ninety-one patient cycles undergoing frozen-thawed blastocyst-stage ET cycles. Live-birth rate. The synthetic protocol used GnRH agonist followed by estrogen and P. The natural protocol used monitoring and post-transfer P. The patients in the two protocols had similar baseline characteristics. Multiple linear regression showed the synthetic protocol to have a higher live-birth rate (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.02-2.09). In patients having two embryos transferred, the synthetic stimulation protocol resulted in a higher live-birth rate per cycle start (32.3% vs. 20.4%; relative risk [RR], 1.58; 95% CI, 1.22-2.06). Similarly, patients with one or two embryos transferred who had additional cryopreserved blastocysts available also had a higher live-birth rate per cycle start (36.1% vs. 12.1; RR, 2.98; 95% CI, 1.16-7.63). The synthetic hormone protocol was associated with a higher live-birth rate when compared with a natural cycle protocol for frozen-thawed blastocyst-stage ET cycles. This improvement persisted when analysis was controlled for cycle cancellation. The synthetic stimulation protocol for frozen-thawed embryo cycles offers improved outcome results for patients.

Noninvasive metabolomic profiling of embryo culture media using proton nuclear magnetic resonance correlates with reproductive potential of embryos in women undergoing in vitro fertilization

To identify biomarkers associated with reproductive outcome using proton nuclear magnetic resonance ((1)H NMR) metabolomic profiling of embryo culture media. Retrospective study. An academic assisted reproductive technology (ART) program; a university research center. Women undergoing ART treatment. Spent media samples from embryos that resulted in pregnancy and delivery (n = 17) and samples (n = 17) from embryos that failed to implant were individually collected on day 3, and evaluated using (1)H NMR spectroscopy. The spectra obtained were quantified by integrating six biomarker signals in the aliphatic region after baseline subtraction. Using a multivariate analysis, a model that calculates a viability index for each spectrum was developed. Sensitivity and specificity of predicting pregnancy (described as implantation and delivery) were calculated. The (1)H NMR metabolomic profile of embryo culture media and embryo viability. Glutamate concentrations determined by (1)H NMR were significantly higher in spent culture media of embryos that resulted in pregnancy and delivery compared to those that failed to implant. Similarly, viability indices calculated by (1)H NMR using the weighted coefficients of glutamate and alanine/lactate ratio quantities were higher for embryos that implanted and resulted in a delivery. Proton NMR spectroscopy predicted viability of individual embryos with a sensitivity of 88.2% and a specificity of 88.2%. Metabolomic profile of spent embryo culture media using (1)H NMR correlates with the reproductive potential of embryos.

Live birth sex ratios are not influenced by blastocyst-stage embryo transfer

To analyze the sex ratio of infants born after blastocyst-stage transfer of embryos with normal preimplantation FISH genetic screening. Retrospective cohort analysis. Large academic assisted reproductive technology center. Two hundred twenty-eight patients undergoing fresh IVF cycle with blastocyst transfer. Preimplantation genetic screening for sex complement. Sex ratio in liveborn infants following blastocyst transfer. One thousand thirteen embryos were normal by preimplantation genetic screening of chromosomes 13, 15, 16, 17, 18, 21, 22, X, and Y. Four hundred ninety-eight normal embryos were transferred to 228 patients with an overall live birth rate of 41.7%. Transferred blastocysts were selected based upon morphologic assessment. When controlling for the sex of the blastocyst embryo, there was no difference in the male-to-female delivery rate per embryo transferred (27.3% vs. 21.4%) (relative risk =1.28, confidence interval 0.93-1.74). Of the live births 51.7% were male and 48.3% were female (P=.61). Subanalysis revealed no difference in male-to-female delivery rates in groups with a 1:1 ratio of male:female embryos transferred, a non 1:1 ratio transferred, or single-sex transfers. Blastocyst-stage embryo transfer does not influence the live birth sex ratio of embryos with normal preimplantation FISH genetic screening.

Assisted reproduction in patients with early-stage ovarian malignancies

Objective To determine the outcome of women with early-stage ovarian malignancies who subsequently underwent assisted reproductive technologies (ART). Design Retrospective study. Setting Academic assisted reproductive technology program. Patient(s) Four infertile women who were previously diagnosed with early-stage ovarian malignancies. Intervention(s) Controlled ovulation hyperstimulation, IVF, and/or gamete intrafallopian transfer treatments using clomiphene citrate and/or gonadotropins. Main outcome measure(s) Development of tumor recurrence and disease-free interval. Result(s) All four women remain free of disease for up to 15 years after treatment. Three of the four women achieved pregnancy. Conclusion(s) In patients with early-stage ovarian malignancies, conservative therapy followed by ovarian stimulation for assisted reproduction is an acceptable strategy.

Early follicular serum müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles

Objective: To test the hypothesis that the concentration of early follicular phase serum müllerian-inhibiting substance (MIS) is associated with ovarian response in women undergoing ovulation induction in preparation for assisted reproductive technology (ART). Design: Retrospective analysis of frozen day 3 serum samples. Setting: Academic ART program. Patient(s): One sample of frozen day 3 serum from women with ≤6 retrieved oocytes (n = 28) compared with women with ≥11 oocytes retrieved (n = 79) in preparation for IVF. Intervention(s): None. Main Outcome Measure(s): Comparison of day 3 serum MIS levels between two groups of women. Other comparisons included maximum serum E 2 concentrations, number of retrieved oocytes, and percentage of mature oocytes between groups. Result(s): Mean serum MIS concentrations were 1.0 ± 0.4 ng/mL compared with 2.5 ± 0.3 ng/mL, or more than a 2.5-fold greater serum concentration of MIS in the group with ≥11 oocytes retrieved compared with in the group with ≤6 retrieved oocytes. Conclusion(s): These data demonstrate an association between early follicular phase serum MIS and the number of retrieved oocytes. Higher day 3 serum MIS concentrations were associated with greater number of retrieved oocytes.

Survival of cryopreservation and thawing with all blastomeres intact identifies multicell embryos with superior frozen embryo transfer outcome

Objective: To assess the impact of survival of cryopreservation and thawing with all blastomeres intact on the outcome of multicell frozen ET. Design: Retrospective study. Setting: Academic assisted reproductive technology program. Patient(s): One hundred sixteen exclusively multicell frozen ETs in 78 patients. Intervention(s): Frozen ET. Main Outcome Measure(s): Relation of embryonic blastomere survival to the outcome of frozen ET (i.e., pregnancy). Result(s): When at least one embryo survived with all blastomeres intact, the total pregnancy rate (biochemical, clinical, or delivered) was 37.7%, the clinical pregnancy rate was 24.6%, and the delivered pregnancy rate was 18.8%. When no embryo survived with all blastomeres intact, the corresponding rates were 10.6%, 8.5%, and 6.4%. The differences in the total pregnancy rate and the clinical pregnancy rate were statistically significant. The delivered pregnancy rates approached statistical significance. Conclusion(s): Multicell embryonic survival of cryopreservation and thawing with all blastomeres intact identifies embryos with superior developmental potential.

Sisters of women with premature ovarian failure may not be ideal ovum donors

Objectives: To determine whether the sisters of women with premature ovarian failure (POF) showed a response to gonadotropin stimulation comparable to that of anonymous ovum donors. Design: Historical cohort study. Setting: Records of 228 consecutive ovum recipients in an academic assisted reproductive technology program. Patient(s): Criteria for inclusion were oocyte recipients age ≤ 40 years, FSH >18 mIU/mL (conversion factor to SI unit, 1.00), and/or failure to respond appropriately to controlled ovarian hyperstimulation (COH). Seventy-nine recipients were classified on the basis of whether they received oocytes from anonymous donors (group I, n = 66) or sister donors (group II, n = 13). Main Outcome Measure(s): Controlled ovarian hyperstimulation response, pregnancy rates (PRs), and implantation rates. Result(s): The ages of the donors to groups I and II were comparable (31.1 ± 16.7 versus 29.8 ± 7.2 years), but those in group II exhibited a higher baseline FSH level (12.8 ± 2.1 versus 8.6 ± 5.8 mIU/mL). Group II versus I had a relative risk of 5.1 for cancellation (4 of 13 [30.8%] versus 4 of 66 [6.1%], respectively). In completed cycles of groups I and II, respectively, there was no difference in serum E 2 on the day of hCG administration (2,356 ± 826 versus 1,847 ± 843 pg/mL; conversion factor to SI unit, 3.671), number of oocytes retrieved (25 ± 14 versus 22 ± 13), number of embryos transferred (4.4 ± 2.1 versus 4.0 ± 1.0), spontaneous abortion rate (22.7% versus 25.0%), PR (35.5% versus 36.4%), and implantation rate (16.2% versus 16.4%). Conclusion(s): There is an increased cancellation rate and, consequently, an overall trend toward decreased ovarian response to gonadotropin stimulation in the sisters of patients with POF. Despite these factors, the implantation rates and PRs of embryos derived from patients reaching retrieval were similar to those from anonymous donors. We recommend counseling women with POF that their sisters may not be ideal ovum donors.

A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program

To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. A randomized clinical trial. Hospital-based academic ART program. A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.