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The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting p values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD (p value < 0.001 at 90 days and p value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both p values < 0.001) and AMH at 90 days (p value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients (p < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women's reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved.

Oocyte Quality Assessment in Breast Cancer: Implications for Fertility Preservation.

BACKGROUND: The aim of this study was to evaluate the effects of breast cancer on the ovarian response and on oocyte quality following controlled ovarian hyperstimulation (COH). METHODS: This retrospective case-control study evaluated the effects of breast cancer on the ovarian response and on the oocyte quality. Oncological patients with breast cancer undergoing controlled ovarian stimulation cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization (IVF) for male or tubal factor infertility were included in the study. Two hundred and ninety-four women were enrolled: 105 affected by breast cancer and 189 healthy women in the control group. Both groups were comparable in terms of age, BMI, and AMH value. Maximal estradiol levels on the triggering day, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, rate of metaphase 2 oocyte production, and numbers of immature and dysmorphic oocytes were analyzed. RESULTS: Considering factors influencing the oocyte quality, such as age, BMI, AMH, duration of stimulation, E2 level on the triggering day, total FSH cumulative dose, stage, histotype, BRCA status, and hormone receptors, the univariate and multivariate analyses identified breast cancer as a risk factor for the presence of dysmorphic oocytes. CONCLUSIONS: The diagnosis of breast cancer does not seem to be associated with the impairment of the ovarian reserve, but is linked to a worsening oocyte quality.

Female fertility preservation: Impact of cancer on ovarian function and oocyte quality.

OBJECTIVE: To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH). METHODS: This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) 22.0. RESULTS: Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P < 0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself. CONCLUSION: Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation.

Oral Antioxidant Treatment of Men Significantly Improves the Reproductive Outcome of IVF Cycles.

Some 30% to 80% of male sub-fertility may be associated with oxidative stress that damages spermatozoa and can decrease success of in vitro fertilization (IVF) techniques. This multicenter, longitudinal, prospective study aimed to investigate whether oral antioxidant supplementation improved the reproductive competence of men who had had low fertilization rates in their previous intracytoplasmic sperm injection (ICSI) cycles without azoospermia or severe oligozoospermia or any identifiable andrological disease. Seventy-seven men from couples who had an ICSI attempt with unexplained <60% fertilization rate took an antioxidant mix of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, and vitamins B2, B6, and B12. Semen parameters were analyzed before (T0) and after 90 days (T90) of treatment, and outcomes of the paired T0 and T90 cycles were compared. After the treatment there was an increase in sperm concentration (p = 0.027), total motile sperm count (p = 0.003), progressive motility (p < 0.0001), and a decreasing trend of DNA-fragmented spermatozoa. Embryological outcomes (fertilization, embryo quality, blastocyst development) were significantly higher in T90 than T0 cycles. No T0 cycle resulted in an evolutive pregnancy. Conversely, in T90 cycles 29 singleton clinical pregnancies were obtained. No negative neonatal outcomes were recorded in newborns after antioxidant treatment. Diet supplementation of men who have had low fertilization rates in their previous ICSI cycles with a combination of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, betaine, and vitamins may improve semen reproductive potential and ICSI clinical outcome.

IUI and uterine lavage of in vivo-produced blastocysts for PGT purposes: is it a technically and ethically reasonable perspective? Is it actually needed?

A recent study by Munné et al. portrayed a protocol to retrieve in vivo produced blastocysts after IUI and uterine lavage for preimplantation genetic testing (PGT) purposes. The authors claimed this protocol might represent a reasonable future perspective for patients who do not want to undergo IVF, but still want to be informed about their embryos' genetic/chromosomal defects. Although the intent of making PGT available also to patients who cannot or do not need to undergo IVF is respectable, the value of this study is undermined by severe technical and ethical issues. Munné and colleagues' paper was discussed within the executive committee (i.e., president and vice-president of the society, director and vice-director of the scientific committee, secretariat, and counselors), the special interest group in reproductive genetics, the scientific committee, and the collegio dei probiviri of the Italian Society of Embryology, Reproduction and Research (SIERR). The points raised from this discussion are summarized in this opinion paper.

Impact of Paternal Age on Seminal Parameters and Reproductive Outcome of Intracytoplasmatic Sperm Injection in Infertile Italian Women.

Background: We conducted a retrospective study on a cohort of couples attending the Department of Andrology and Reproductive Physiopathology at Sandro Pertini Hospital in Rome for Intracytoplasmatic Sperm Injection (ICSI)-assisted reproduction programs. Some of the couples included in the study underwent more than one ICSI cycle. Between January 2015 and April 2017. Objective: To evaluate whether the advancing of the paternal age may have effect on the seminal parameters, thus negatively affecting the embryo formation, development and quality, as well as the pregnancy rate. Materials and Methods: Five hundred and forty three ICSI cycles were performed on 439 couples undergoing Assisted Reproductive Technologies (ART). Patients were subdivided into three male and three female age groups having similar size: Men: ≤38 years (MI), 39-43 years (MII), ≥44 years (MIII). Women: ≤35 years (FI), 36-40 years (FII),≥41 years (FIII). Discussion and Conclusion: Male age groups did not reveal any statistical significant differences in any age-related semen parameters. We also confirmed a statistical significant increase in the pregnancy rate of couples with older partner age difference and younger female. We found that the advanced male age increases the probability of obtaining one or no type A embryo (NA≤1), which was almost doubled in the MIII group in comparison with MI, suggesting a negative effect of male age on the efficacy of the reproductive outcome in terms of a reduced number of type A embryos. Such an effect does not seem related to semen parameters and may deserve further investigations.

Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial.

The aim of this prospective randomized study was to assess the advantages of a new modified intracytoplasmic sperm injection (ICSI) technique called intracytoplasmic morphologically selected sperm injection (IMSI) over the conventional ICSI procedure in the treatment of patients with severe oligoasthenoteratozoospermia. The new procedure consisted of IMSI based on a preliminary motile sperm organellar morphology examination under x6600 high magnification. A total of 446 couples with at least two previous diagnoses of severe oligoasthenoteratozoospermia, 3 years of primary infertility, the woman aged 35 years or younger, and an undetected female factor were randomized to IVF micro-insemination treatments: ICSI (n = 219; group 1) and IMSI (n = 227; group 2). A comparison between the two different techniques was made in terms of pregnancy, miscarriage and implantation rates. The data showed that IMSI resulted in a higher clinical pregnancy rate (39.2% versus 26.5%; P = 0.004) than ICSI when applied to severe male infertility cases. Despite their initial poor reproductive prognosis, patients with two or more previous failed attempts benefited the most from IMSI in terms of pregnancy (29.8% versus 12.9%; P = 0.017) and miscarriage rates (17.4% versus 37.5%). At present, 35 healthy babies have been born following the introduction of this promising technique in daily IVF practice.

Cryotop vitrification of human oocytes results in high survival rate and healthy deliveries.

Vitrification, an ultra-rapid cooling technique, offers a new perspective in attempts to develop an optimal cryopreservation procedure for human oocytes and embryos. To further evaluate this method for human oocytes, 796 mature oocytes (metaphase II) were collected from 120 volunteers. Since Italian legislation allows the fertilization of a maximum of only three oocytes per woman, there were 463 supernumerary oocytes; instead of being discarded, they were vitrified. When, in subsequent cycles, these oocytes were utilized, 328 out of 330 (99.4%) oocytes survived the warming procedure. The fertilization rate, pregnancy rate and implantation rate per embryo were 92.9, 32.5 and 13.2% respectively. Thus, as already reported in the literature, the vitrification procedure seems to be highly effective, safe (since healthy babies have been born) and easy to apply. In situations where embryo cryopreservation is not permitted (as in Italy), there is now good indication for routine application of the method, once further standardization is achieved.

Refinement techniques in experimental protocols involving Callitrichids.

The invasiveness of biomedical experiments on laboratory animals should be limited to the greatest extent possible yet without sacrificing the quality of the data collected. To this end, refinement techniques can be used. In the present work, we describe some of these techniques, focussing on the familiarity of the experimental environment, alternative sampling techniques (including the use of positive training), telemetry, and methods for improving ethological experiments. As a model, we have chosen the common marmoset (Callithrix jacchus), which is frequently used in biomedical research.