Male factor infertility and assisted reproductive technologies: indications, minimum access criteria and outcomes.

BACKGROUND: Infertility, which is defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourses, affects about 15-20% of couples worldwide and a male factor is involved in about half of the cases. The development of assisted reproductive technology (ART) made it possible to conceive also to individuals affected from severe oligospermia or azoospermia. However, the impact of the male factor on embryo development, implantation, prevalence of chromosomal abnormalities, genetic and epigenetic alterations, and clinical and obstetric outcomes is still controversial. PURPOSE: This narrative review examines the indications, minimum access criteria, and outcomes by individual ART technique in relation to the male factor.

The effect of extended cryo-storage following vitrification on embryo competence: a systematic review and meta-analysis.

PURPOSE: Few studies explored whether prolonged cryo-storage after vitrification affects embryo competence and perinatal outcomes. This systematic review and meta-analysis aims at highlighting any putative impact of cryo-storage duration on cryo-survival, miscarriage, live birth and major malformations. METHODS: A systematic review was performed using MEDLINE (PubMed), ISI Web of Knowledge, Scopus and Embase databases up to June 2021. Data were combined to obtain a pooled OR, and meta-analysis was conducted using a random effects model. Out of 1,389 screened abstracts, 22 papers were assessed for eligibility, and 5 studies were included (N = 18,047 embryos). Prolonged cryo-storage was defined as > 12 months (N = 3389 embryos). Subgroup analysis was performed for untested vitrified cleavage stage embryos (N = 1739 embryos) and for untested and euploid vitrified blastocysts (N = 13,596 and 2712 embryos, respectively). RESULTS: Survival rate, miscarriage, live birth and major malformation rates were all similar in the two groups. CONCLUSION: These data further support the safety of long-term cryo-storage of human embryos beyond 12 months. This is reassuring for good prognosis patients with surplus embryos, couples seeking a second child from supernumerary embryos and women postponing the transfer for clinical or personal reasons.

Clinical validity and utility of preconception expanded carrier screening for the management of reproductive genetic risk in IVF and general population.

STUDY QUESTION: What is the clinical validity and utility of preconception Expanded Carrier Screening (ECS) application on the management of prospective parents? SUMMARY ANSWER: The high detection rate of at-risk couples (ARCs) and the high proportion opting for IVF/preimplantation genetic testing (PGT) treatment demonstrate the clinical utility of ECS in the preconception space in IVF and general population. WHAT IS KNOWN ALREADY: About 2-4% of couples are at risk of conceiving a child with an autosomal recessive or X-linked genetic disorder. In recent years, the increasing cost-effectiveness of genetic diagnostic techniques has allowed the creation of ECS panels for the simultaneous detection of multiple recessive disorders. Comprehensive preconception genetic screening holds the potential to significantly improve couple's genetic risk assessment and reproductive planning to avoid detectable inheritable genetic offspring. STUDY DESIGN, SIZE, DURATION: A total of 3877 individuals without a family history of genetic conditions were analyzed between January 2017 and January 2020. Of the enrolled individuals, 1212 were gamete donors and 2665 were patients planning on conceiving from both the IVF and the natural conception group. From the non-donor cohort, 1133 were analyzed as individual patients, while the remaining ones were analyzed as couples, for a total of 766 couples. PARTICIPANTS/MATERIALS, SETTING, METHODS: A focused ECS panel was developed following American College of Obstetrics and Gynecology ACOG-recommended criteria (prevalence, carrier rate, severity), including highly penetrant severe childhood conditions. Couples were defined at-risk when both partners carried an autosomal recessive pathogenic/likely pathogenic variant (PLP) on the same gene or when the woman was a carrier of an X-linked PLP variant. ARC detection rate defined the clinical validity of the ECS approach. Clinical utility was evaluated by monitoring ARCs reproductive decision making. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 402 individuals (10.4%) showed PLP for at least one of the genes tested. Among the 766 couples tested, 173 showed one carrier partner (22.6%), whereas 20 couples (2.6%) were found to be at increased risk. Interestingly, one ARC was identified as a result of cascade testing in the extended family of an individual carrying a pathogenic variant on the Survival Of Motor Neuron 1SMN1 gene. Of the identified ARCs, 5 (0.7%) were at risk for cystic fibrosis, 5 (0.7%) for fragile X syndrome, 4 (0.5%) for spinal muscular atrophy, 4 (0.5%) for Beta-Thalassemia/Sickle Cell Anemia, 1 (0.1%) for Smith-Lemli-Opitz Syndrome and 1 (0.1%) for Duchenne/Becker Dystrophy. Fifteen ARCs were successfully followed up from both the IVF and the natural conception groups. All of these (15/15) modified their reproductive planning by undergoing ART with Preimplantation Genetic Testing for Monogenic disease and Aneuploidies (PGT-M and PGT-A). To date, 6/15 (40%) couples completed their PGT cycle with euploid/unaffected embryos achieving a pregnancy after embryo transfer and three of them have already had an unaffected baby. LIMITATIONS, REASONS FOR CAUTION: The use of a limited panel of core gene-disease pairs represents a limitation on the research perspective as it can underestimate the rate of detectable carriers and ARCs in this cohort of prospective parents. Expanding the scope of ECS to a larger panel of conditions is becoming increasingly feasible, thanks to a persistent technological evolution and progressive cataloging of gene-disease associations. WIDER IMPLICATIONS OF THE FINDINGS: These results highlight the potential clinical validity and utility of ECS in reducing the risk of a pregnancy affected by a detectable inheritable genetic condition. The steady reduction in the costs of genetic analyses enables the expansion of monogenic testing/screening applications at the preimplantation stage, thus, providing valid decisional support and reproductive autonomy to patients, particularly in the context of IVF. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. A.C., M.F., S.C., M.P., L.G., and C.P. are employees of Igenomix Italy. C.S. is the head of the scientific board of Igenomix. TRIAL REGISTRATION NUMBER: N/A.

Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study.

Male infertility is a multifactorial disorder that affects a significant percentage of couples. Its etiology and pathogenesis remain elusive in about one-third of the cases; this is referred to as idiopathic infertility. Inositols mediate the sperm processes involved into oocyte fertilization, such as penetration of the ovum cumulus oophorus, binding with the zona pellucida and the acrosome reaction. The aim of this double-blind, randomized, placebo-controlled trial was to evaluate the efficacy and safety of myoinositol (the most abundant form of inositols present in nature) treatment in men with idiopathic infertility. To accomplish this, we evaluated the effects of myoinositol on sperm parameters and reproductive hormones at baseline and after 3 months of treatment in men with idiopathic infertility. No adverse reaction was observed. Myoinositol significantly increased the percentage of acrosome-reacted spermatozoa, sperm concentration, and total count and progressive motility compared to placebo. In addition, myoinositol rebalanced serum luteinizing hormone, follicle-stimulating hormone, and inhibin B concentrations. The clinical improvement of idiopathic infertile patients should encourage myoinositol use for the treatment of this disorder, even though its detailed mechanisms at the testicular level remain still unclear.

Oral contraceptives and changes in nutritional requirements.

Oral contraceptives (OCs) are a major class of prescription drug, used by a large proportion of women starting from early adolescence. Much research has been conducted to investigate the physiological changes that occur in women who take OCs. These include changes in general health as well as in nutritional needs. In terms of nutrition, several studies investigated whether women on OCs need different amounts of some vitamins and minerals. In particular, a report from the World Health Organization (WHO) points out that the influence of OCs on nutrient requirements is a topic of high clinical relevance and should, therefore, receive great attention. It has been shown that the key nutrient depletions concern folic acid, vitamins B2, B6, B12, vitamin C and E and the minerals magnesium, selenium and zinc. Most research has focused on the levels of these vitamins and minerals in the blood of women who take OCs compared to women who do not. Since women who take OCs not always have adequate diet, may have unhealthy life style or may suffer from pathologies of malabsorption, the possibility to prevent vitamin and mineral deficiencies by taking appropriate dietary supplements should be considered a first-line approach by clinicians.

Bye-bye chiro-inositol - myo-inositol: true progress in the treatment of polycystic ovary syndrome and ovulation induction.

Polycystic ovary syndrome (PCOS) is a multifactorial syndrome affecting 10% of women in reproductive age. Insulin sensitizer agents are the best therapeutic option for PCOS patients; among which there is Inositol. Inositol is a polyalcohol existing as nine different stereoisomers, two of which have been shown to be insulin mediators: myo-inositol (MI) and D-chiro-inositol (DCI). So far only MI have been show to be present in the follicular fluid and in a direct comparison between MI and DCI only MI was able to improve oocyte and embryo quality. Therefore, Could we say "bye-bye D-chiro-Inositol" in the practice of clinical gynecology and reproductive medicine?

Uterine myomas during pregnancy: a longitudinal sonographic study.

OBJECTIVE: To evaluate volumetric changes of uterine myomas (fibroids) during pregnancy. METHODS: This was an observational, longitudinal and prospective study of 38 consecutive Caucasian women with singleton pregnancies and a total of 42 uterine myomas, enrolled from a cohort of 1492 women who took part in our first-trimester Down syndrome screening program. Myoma volume was evaluated by ultrasound at 11-14, 20-22 and 32-34 weeks of gestation. RESULTS: Mean myoma volume increased significantly throughout pregnancy. Taking a volumetric change of > 10% between gestational periods to be an increase in size, 71.4% of uterine myomas increased in size between the first and second gestational periods, while this percentage was slightly lower (66.6%) between the second and third periods. Logistic regression analysis revealed that greater maternal age was correlated with a reduction/no change in overall myoma size and multiparity was correlated with a decrease/no change between the first and second trimesters, while a higher prepregnancy maternal body mass index (BMI) was correlated with a volumetric increase between the first and second trimesters and a decrease/no change between the second and third trimesters. CONCLUSIONS: Fibroids enlarge during pregnancy regardless of their initial size or local factors, and maternal age, prepregnancy BMI and parity are apparently correlated with these changes.