Reply to Cetkovic et al. Comment on "Meneghini et al. The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF. Nutrients 2023, 15, 4444".

Thanks for your comment [...].

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.

Use of follicle-stimulating hormone for the male partner of idiopathic infertile couples in Italy: Results from a multicentre, observational, clinical practice survey.

BACKGROUND: The management of male idiopathic infertility is heterogeneous. Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH < 8 IU/L, independently of semen parameters. AIM: Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment. METHODS: A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age >18 years and FSH serum levels <8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner. RESULTS: A total of 718 infertile couples were enrolled, and 241 patients were re-evaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P < .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P < .001) and teratozoospermia from 43.6% to 27.7% (P < .001). DISCUSSION: This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events.

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.

Sperm glyceraldehyde 3-phosphate dehydrogenase gene expression in asthenozoospermic spermatozoa.

It has been suggested that the energy required for sperm motility is produced by oxidative phosphorylation while glycolysis seems to be an important source for ATP transmission along the flagellum. Some studies have investigated the chemical and kinetic properties of the enzyme glyceraldehyde 3-phosphate dehydrogenase to identify any changes in the regulation of glycolysis and sperm motility. In contrast, there are few studies analyzing the genetic basis of hypokinesis. For this reason, we investigated the glyceraldehyde 3-phosphate dehydrogenase gene in human sperm to evaluate whether asthenozoospermia was correlated with any changes in its expression. Semen examination and glyceraldehyde 3-phosphate dehydrogenase gene expression studies were carried out on 116 semen samples divided into two groups - Group A consisted of 58 normokinetic samples and Group B of 58 hypokinetic samples. Total RNA was extracted from spermatozoa, and real-time PCR quantification of mRNA was carried out using specific primers and probes. The expression profiles for the Groups A and B were very similar. The mean delta Ct was as follows - Group A, 5.79 ± 1.04; Group B, 5.47 ± 1.27. Our study shows that in human sperm, there is no difference in glyceraldehyde 3-phosphate dehydrogenase gene expression between samples with impaired motility and samples with normal kinetics. We believe that this study could help in the understanding of the molecular mechanisms of sperm kinetics, suggesting that hypomotility may be due to a possible posttranscriptional impairment of the control mechanism, such as mRNA splicing, or to posttranslational changes.

Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action.

In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action.

Mitochondrial membrane potential profile and its correlation with increasing sperm motility.

OBJECTIVE: To investigate sperm mitochondrial integrity through analysis of mitochondrial membrane potential (Δψ) and to correlate the energy status with variations in sperm motility. DESIGN: Experimental study. SETTING: Seminology Laboratory, University of Rome, Italy. PATIENT(S): Two hundred thirteen semen samples from the same number of patients, divided into two groups on the basis of their motility: group A, 185 samples with linear motility and group B, 28 samples with nonlinear motility. INTERVENTION(S): Evaluation of sperm motility. MAIN OUTCOME MEASURE(S): Sperm mitochondrial integrity evaluated with a fluorimetric method using the cationic lipophilic stain JC-1. RESULT(S): The mean FL2 (percentage of sperm with high and low ∆ψ) for group A was 46.19±23.25 and for group B, it was 48.32±24.43. There was no significant difference between the groups. There was a positive correlation between both FL2 and linear motility and FL2 and sperm vitality in group A; both correlations were statistically significant. In group B, there was a positive correlation between FL2 and nonlinear motility and FL2 and sperm vitality; again, both correlations were statistically significant. CONCLUSION(S): Our data reveal a positive correlation between total motility and Δψ, suggesting that sperm motility may be dependent on the functional integrity of the mitochondria.

Testicular tumors as a possible cause of antisperm autoimmune response.

OBJECTIVE: To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month after orchiectomy and before radiotherapy or chemotherapy. DESIGN: Clinical study. SETTING: Department of andrology and seminology at a university hospital. PATIENT(S): One hundred ninety patients with testicular cancer. INTERVENTION(S): Determination of semen parameters and autoimmune reaction evaluated on the sperm surface and in blood serum. MAIN OUTCOME MEASURE(S): Autoimmune reaction on the sperm surface by the direct immunobead test (IBT), and in blood serum by the indirect IBT and the gelatin agglutination test (GAT), was evaluated 1 month after orchiectomy and before beginning chemotherapy or radiotherapy. RESULT(S): Of the 190 patients, 11 (5.8%) were positive for antisperm antibody by GAT. On indirect IBT, 3 of the 11 GAT-positive patients were positive to IgG class only, with values of 22%, 24%, and 40%. Of the 11 GAT-positive patients, 4 showed no antibody bound to the sperm surface, and 3 were positive to IgG class only (28%, 21%, and 38%), with binding exclusively on the tail. Direct IBT could not be performed in the remaining 4 patients. CONCLUSION(S): Our data support the hypothesis that testicular cancer might not be a possible cause of antisperm autoimmunization and infertility.