Biallelic variants in ZFP36L2 cause female infertility characterised by recurrent preimplantation embryo arrest

BackgroundRecurrent preimplantation embryo developmental arrest (RPEA) is the most common cause of assisted reproductive technology treatment failure associated with identified genetic abnormalities. Variants in known maternal genes can only account for 20%–30% of these cases. The underlying genetic causes for the other affected individuals remain unknown.MethodsWhole exome sequencing was performed for 100 independent infertile females that experienced RPEA. Functional characterisations of the identified candidate disease-causative variants were validated by Sanger sequencing, bioinformatics and in vitro functional analyses, and single-cell RNA sequencing of zygotes.ResultsBiallelic variants in ZFP36L2 were associated with RPEA and the recurrent variant (p.Ser308_Ser310del) prevented maternal mRNA decay in zygotes and HeLa cells.ConclusionThese findings emphasise the relevance of the relationship between maternal mRNA decay and human preimplantation embryo development and highlight a novel gene potentially responsible for RPEA, which may facilitate genetic diagnoses.

Quality of Life in Infertile People Forced to Suspend Assisted Reproductive Technology Treatment during the COVID-19 Global Health Emergency

To evaluate the psycho-physical well-being of people coping with infertility who were forced to suspend ART treatment due to restrictions related to the COVID-19 global health emergency.

Hyperreactio luteinalis following frozen embryo transfer managed by fetal reduction

We report a rare case of hyperreactio luteinalis (HL) which developed in association with triplet pregnancy in a 27-year-old woman who underwent assisted reproductive technology treatment for primary infertility. She had undergone frozen embryo transfer 2 months after ovarian retrieval. She presented in the first trimester with abdominal pain and distension associated with ovarian enlargement and did not respond to conservative management. Fetal reduction was done from triplets to twins which resulted in good symptomatic relief for the patient. Fetal reduction may be an effective approach in such situations when conservative strategies fail in HL.

Pre-Conception Interventions for Subfertile Couples Undergoing Assisted Reproductive Technology Treatment: Modeling Analysis

Background Approximately 1 in 7 couples experience subfertility, many of whom have lifestyles that negatively affect fertility, such as poor nutrition, low physical activity, obesity, smoking, or alcohol consumption. Reducing lifestyle risk factors prior to pregnancy or assisted reproductive technology treatment contributes to the improvement of reproductive health, but cost-implications are unknown. Objective The goal of this study was to evaluate reproductive, maternal pregnancy, and birth outcomes, as well as the costs of pre-conception lifestyle intervention programs in subfertile couples and obese women undergoing assisted reproductive technology. Methods Using a hypothetical model based on quantitative parameters from published literature and expert opinion, we evaluated the following lifestyle intervention programs: (1) Smarter Pregnancy, an online tool; (2) LIFEstyle, which provides outpatient support for obese women; (3) concurrent use of both Smarter Pregnancy and LIFEstyle for obese women; (4) smoking cessation in men; and (5) a mindfulness mental health support program using group therapy sessions. The model population was based on data from the Netherlands. Results All model-based analyses of the lifestyle interventions showed a reduction in the number of in vitro fertilization, intracytoplasmic sperm injection, or intrauterine insemination treatments required to achieve pregnancy and successful birth for couples in the Netherlands. Smarter Pregnancy was modeled to have the largest increase in spontaneous pregnancy rate (13.0%) and the largest absolute reduction in potential assisted reproductive technology treatments. Among obese subfertile women, LIFEstyle was modeled to show a reduction in the occurrence of gestational diabetes, maternal hypertensive pregnancy complications, and preterm births by 4.4%, 3.8%, and 3.0%, respectively, per couple. Modeled cost savings per couple per year were €41 (US $48.66), €360 (US $427.23), €513 (US $608.80), €586 (US $695.43), and €1163 (US $1380.18) for smoking cessation, mindfulness, Smarter Pregnancy, combined Smarter Pregnancy AND LIFEstyle, and LIFEstyle interventions, respectively. Conclusions Although we modeled the potential impact on reproductive outcomes and costs of fertility treatment rather than collecting real-world data, our model suggests that of the lifestyle interventions for encouraging healthier behaviors, all are likely to be cost effective and appear to have positive effects on reproductive, maternal pregnancy, and birth outcomes. Further real-world data are required to determine the cost-effectiveness of pre-conception lifestyle interventions, including mobile apps and web-based tools that help improve lifestyle, and their effects on reproductive health. We believe that further implementation of the lifestyle app Smarter Pregnancy designed for subfertile couples seeking assistance to become pregnant is likely to be cost-effective and would allow reproductive health outcomes to be collected.