The Impact of Unbalanced Maternal Nutritional Intakes on Oocyte Mitochondrial Activity: Implications for Reproductive Function

Accumulating evidence on the effect of nutrition on reproduction is emerging from both animal and human studies. A healthy dietary pattern and nutrient supplementation, especially during the peri-conceptional period, might be helpful to achieve a live birth, although the mechanisms implicated are not fully understood. The endocrine system and the ooplasmic organelles apparatus, in particular the mitochondria, are clearly key elements during oogenesis and subsequent embryo development, and their proper functioning is associated with nutrition, even beyond maternal aging. Several studies in animal models have reported various adverse effects on mitochondria caused by unbalanced dietary intakes such as high fat diet, high fat high sugar diet, and low protein diet. The alterations produced might include mitochondrial intracellular distribution, content, structure, biogenesis, and functioning. This review summarizes the key role of mitochondria in female reproduction and the effects of different dietary macronutrient compositions on oocyte mitochondrial activity with their possible short-, medium-, and long-term effects

A brief history of oocyte cryopreservation: Arguments and facts

: The term "cryopreservation" refers to the process of cooling cells and tissues and storing them at subzero temperatures in order to stop all biological activity and preserve their viability and physiological competences for future use. Cooling to subzero temperatures is not a physiological condition for human cells; this is probably due to the high content of water in the living matter, whose conversion to ice crystals may be associated with severe and irreversible damage. Among reproductive cells and tissues, metaphase II oocytes are notably vulnerable to cryopreservation, mainly because of their large size, low surface area to volume ratio, relatively high water content and presence of the meiotic spindle. As human biological systems lack efficient internal defense mechanisms against chilling injuries, it is of the utmost importance to supply adequate external support, in terms of cryoprotectant additives, appropriate cooling/warming rates, and suitable long-term storage. Over the years, scientists have proposed different cryopreservation strategies in the effort to achieve an optimized recipe ensuring cell survival and, at the same time, maintenance of the physiological functions and abilities necessary to continue life. However, despite the first success obtained in the 1980s with frozen oocytes, it was not until recently that notable improvements in the cryopreservation technique, thanks to the advent of vitrification, allowed a breakthrough of this fine procedure

Endometriosis shows no impact on the euploid blastocyst rate per cohort of inseminated metaphase-II oocytes: A case-control study

Objective: To evaluate the true impact of endometriosis on oocytes' competence defined as blastulation, euploidy and implantation rates. Design: Retrospective multicenter case-control study involving infertile couples undergoing ICSI with qPCR and trophectoderm biopsy-based PGT-A. Patients affected from endometriosis (n = 210) were diagnosed through transvaginal sonography or surgical history with histological confirmation. Each case was matched to two controls (n = 420) according to IVF clinic, maternal age at retrieval (38.6 ± 2.7 yr), number of previous failed IVF treatments (0.5 ± 0.8) and number of metaphase-II oocytes retrieved (6.1 ± 3.7 per patient). The primary outcome was the mean euploid blastocyst rate per cohort of inseminated metaphase-II oocytes. Other embryological, clinical, obstetric and neonatal outcomes were also evaluated. Results: The mean euploid blastocyst rate per cohort of inseminated metaphase-II oocytes was identical in the two groups (18 %±22 %) independently of maternal age. No difference was shown for all embryological outcomes investigated. The live birth rates per vitrified-warmed single euploid blastocyst transfer were also similar (67/158, 42 % in patients affected from endometriosis versus 132/327, 40 % in matched-controls). No difference was reported in the gestational and neonatal outcomes. The cumulative live birth delivery rates among completed cycles were also identical (61/201, 30 % versus 117/391, 30 % in endometriosis and matched-control groups, respectively) independently of maternal age. Conclusions: Endometriosis might not impair oocyte developmental and reproductive competence, although its potential impact on the number of metaphase-II oocytes retrieved cannot be ignored. This information is critical for clinicians during counseling to outline an effective strategy to treat infertile patients affected from this condition. Future prospective studies are needed to evaluate the impact of endometriosis stage on euploidy rates

Maternal body mass index associates with blastocyst euploidy and live birth rates: the tip of an iceberg?

Research question: Does maternal preconceptional body mass index (BMI) associate with mean blastocyst euploidy rate (m-ER) per patient and live birth rate (LBR) after vitrified-warmed euploid single embryo transfer (SET)? Design: Observational study conducted between April 2013 and March 2020 at a private IVF clinic, involving 1811 Caucasian women undergoing trophectoderm biopsy and comprehensive chromosome testing. The outcomes of 1125 first vitrified-warmed euploid SET were also analysed. Patients were clustered as normal weight (BMI 18.5-25; n = 1392 performing 859 SET), underweight (BMI <18.5; n = 160 performing 112 SET) and overweight (BMI >25; n = 259 performing 154 SET). m-ER per patient was the primary outcome. The secondary outcomes were all clinical outcomes per euploid SET. All data were adjusted for confounders through regression analyses. Results: The m-ER per patient decreases as maternal BMI increases from 17 up to 22-23 before reaching a plateau. A linear regression adjusted for maternal age confirmed this moderate association (unstandardized coefficient B: -0.6%, 95% confidence interval [CI]: -1.1 to -0.1%, P = 0.02). All clinical outcomes were similar between normal weight and underweight women. Overweight women, instead, showed higher miscarriage rate per clinical pregnancy (n = 20/75, 26.7% versus n = 67/461, 14.5%; odds ratio [OR] adjusted for blastocyst quality and day of full blastulation: 2.0, 95% CI: 1.1-3.6, P = 0.01) and lower LBR per SET (n = 55/154, 35.7% versus n = 388/859, 45.2%; OR adjusted for blastocyst quality and day of full blastulation: 0.67, 95% CI: 0.46-0.96, P = 0.03). Conclusion: These data indicate a need for future research on more sensitive metrics to assess body fat mass and distribution, as well as on the mechanisms leading to lipotoxicity, thereby impairing embryo competence and/or endometrial receptivity. Overweight women should be informed of their higher risk for miscarriage and, whenever possible, encouraged to lose weight, especially before transfer