First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility.

OBJECTIVES: To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated in vitro fertilization (IVF) failures for the treatment of idiopathic infertility. DESIGN: A prospective pilot study. SETTING: IVF center. PATIENT(S): Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3-11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. INTERVENTION(S): We performed MST by transferring metaphase II spindles from the patients' oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, in vitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. MAIN OUTCOME MEASURE(S): Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. RESULT(S): Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12-24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. CONCLUSION(S): This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. CLINICAL TRIAL REGISTRATION NUMBER: Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.

Correlation of serum anti-Müllerian hormone levels with positive in vitro fertilization outcome using a short agonist protocol.

OBJECTIVE: We examined the predictive ability of anti-Müllerian hormone (AMH) for clinical pregnancy in women who underwent in vitro fertilization (IVF) cycles in a short agonist protocol. DESIGN: This is a retrospective cohort study of 222 women undergoing their first IVF attempt between June 2010 and March 2016. Multivariate logistic regression analysis was performed to evaluate the independent associations between clinical pregnancy and its possible predictors. RESULTS: 14.9% of cycles were cancelled, >3 oocytes were retrieved in 55.4% of cycles and embryo transfer was performed in 70.7% of cases. Live birth was the final outcome in 19.8% of subjects, miscarriage occurred in 4.1%, whereas no pregnancy occurred in the remaining 76.1% of the study sample. The number of oocytes, number of embryos, embryo transfer rate and pregnancy rates were positively associated with serum AMH concentrations (p <0.001, for each association). When analyzed by age quartiles, the overall association between AMH and clinical pregnancy rates was evident across all age strata. CONCLUSIONS: Serum AMH levels are a strong predictive marker of clinical pregnancy in women undergoing a short agonist IVF protocol. There is also a strong association with cancellation rate, number of oocytes retrieved, poor response (≤3 oocytes), number of embryos, embryo transfer rate and live birth rates.