Fertility preservation in women with endometriosis: Oocyte cryopreservation and other techniques.

In recent years, advancements in cryopreservation techniques for oocytes, embryos, and ovarian tissue have enabled offering fertility preservation (FP) options to women with endometriosis. It is recommended to always conduct specialized counselling on FP, especially before considering surgical interventions for endometriosis. The decision regarding the methods of FP, the timing, and to which women affected by endometriosis these techniques should be offered are still subjects of discussion. However, several studies suggest that it can be proposed before surgical interventions for endometriosis, particularly if the patient is undergoing mono or bilateral endometrioma surgery. The most recommended technique is ovarian stimulation, followed by oocyte cryopreservation. Nevertheless, the literature contains various studies describing FP through embryo cryopreservation or the retrieval and cryopreservation of ovarian tissue.

Impact of surgery for endometriosis on the outcomes of in vitro fertilization.

This narrative review aims to summarize available evidence on the IVF-associated outcomes after surgery for endometriosis. Only one retrospective study investigated if surgical treatment of superficial/peritoneal endometriosis may modify the outcomes of IVF; therefore, more data are needed to confirm the benefit of surgery for this type of disease for improving ART outcomes, and to be able to support it in routine practice. Solid evidence from several meta-analyses demonstrates that surgical treatment of endometriomas does not enhance the outcomes of IVF. In contrast, surgical treatment of ovarian endometriosis may lead to a reduction in ovarian reserve, especially in cases involving bilateral endometriomas or repeated surgical procedures. Some non-randomized studies have examined if surgical treatment on deep endometriosis may influence IVF outcomes. A systematic review with meta-analysis revealed that patients who underwent surgery before IVF exhibited significantly higher pregnancy rates per patient, pregnancy rates per cycle, and live birth rates per patient compared to those without prior surgery. However, the available data are insufficient to recommend surgical excision of deep endometriosis as the first-line treatment for asymptomatic patients to enhance IVF outcomes.

Algorithm vs. clinical experience: controlled ovarian stimulations with follitropin-delta and individualised doses of follitropin-alpha/beta.

In the registrational trials, follitropin delta was compared with a fixed dose of 150 UI of follitropin alpha/beta, finding higher chances to reach a target response of 8-14 oocytes compared to controls. For this reason, follitropin delta is marketed as particularly useful in expected hyper-responder patients. The main outcome of this study is to report if comparable results are reached in a real-life scenario with follitropin alpha/beta personalized doses, based on patients' characteristics. This is a retrospective study performed in two public fertility centres. All first cycles from January 2020 to June 2022 with either follitropin delta (cases) or alpha/beta (controls) in patients with antiMüllerian hormone >2.5 ng/ml were compared by an inverse probability weighting approach based on propensity score. The follitropin total dose was higher in controls (1179.06 ± 344.93 vs. 1668.67 ± 555.22 IU, p<0.001). The target response of 8-14 oocytes was reached by 40.2% of cases and 40.7% of controls (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.65-1.53, p=0.98). Fewer than 8 oocytes were collected in 24.1% of cases and 22% of controls (OR 1.10, 95% CI 0.71-1.69, p=0.67); more than 14 oocytes in 35.7% of cases and 37.3% of controls (OR 0.83, 95% CI 0.54-1.28, p=0.40). Our experience did not find worse results in term of proportion of patients who reached the target response with an algorithm-chosen dose of follitropin delta compared to a personalised starting dose of follitropin alpha/beta, with follitropin delta having the advantage of objectivity. Larger numbers are needed to confirm these results.

Oxidative Stress: The Role of Estrogen and Progesterone.

The effect of estrogen and progesterone on oxidative status is not yet very clear, improvements and detrimental effects having been reported with the use of menopausal hormone therapy or hormonal contraceptives, respectively. In this study, we evaluated the role played by estrogen and progesterone separately, on the oxidative status of 32 women, 18 to 43 years old, by inducing high levels of estrogen and then adding high levels of progesterone. During a cycle of in vitro fertilization, blood samples were collected prior to gonadotrophin stimulation (low estradiol levels), on the day of oocyte retrieval (high levels of estrogen), and on the day of embryo transfer (high levels of estrogen and progesterone). Total blood levels of oxidants (FORT), antioxidants (FORD), and their ratio FORT/FORD were measured using a colorimetric method based on the Fenton reaction. Seven women measured their early morning body temperature at the same time points. FORT significantly decreased from the low- to the high-estrogen phase (p = 0.023) and increased from the high-estrogen to the high-estrogen-progesterone phase (p = 0.006). FORD showed an opposite but non-significant trend. The FORT/FORD ratio decreased from the low- to the high-estrogen phase (p = 0.0104) and increased from the high-estrogen to the high-estrogen -progesterone phase (p = 0.004). Body temperature (n = 7) decreased in the high-estrogen phase (p = 0.001) and increased from the high-estrogen to the high-estrogen-progesterone phase (p = 0.001). In the seven women, FORT (p = 0.009) and FORT/FORD (p = 0.0056) were linearly related to body temperature values. Our data show opposite effects of estrogen and progesterone on oxidative status. These effects seem to be related to the effect exerted on body temperature regulation.

Collecting semen samples at home for fertility assessment: time for a new standard?

BACKGROUND: In fertility clinics the standard approach to semen collection involves a private room close to the laboratory to avoid fluctuations in temperature and to control the time between collection and processing. There are still no firm conclusions whether collecting semen at home has any influence on sperm quality and reproductive competence. The purpose of this study was to assess whether the site of semen collection affects semen parameters. METHODS: This retrospective cohort study performed at a tertiary level public fertility center included 8634 semen samples from 5880 men undergoing fertility assessment from 2015 to 2021. The impact of sample collection site was evaluated using a generalized linear mixed model. A subgroup analysis comparing clinic to home collection within the same patient was performed on 1260 samples from 428 men by paired t-test or Wilcoxon Signed Rank Test. RESULTS: Samples collected at home (N.=3240) had significantly higher semen volume, sperm concentration and total sperm count respect to samples collected at clinic (N.=5530) (median (range): 2.9 (0.0-13.9) mL versus 2.9 (0.0-11.5) mL, P=0.016; 24.0 (0.0-252.0) million/mL versus 18.0 (0.0-390.0), P<0.0001; 64.6 (0.0-946.0) million versus 49.3 (0.0-1045.0), P<0.0001, respectively). There was no difference in abstinence period and sperm motility. Paired comparisons of semen characteristics in 428 patients with home-collected (N.=583) and clinic-collected (N.=677) samples confirmed a no negative effect on volume and total sperm count. CONCLUSIONS: Our data provide evidence for a not disadvantage with collection at home.

Pregnancy complications after allogeneic hematopoietic stem cells transplantation: Focus on the placenta.

INTRODUCTION: hematopoietic stem cells transplantation (HSCT) is a treatment option for malignant and non-malignant haematological diseases. Because of the improved survival rates and the more widespread use of reproductive technologies in the last two decades, the number of patients who conceive is increasing while the pathogenesis of some obstetrical complications observed is not yet fully clarified. METHODS: we present complete data about two pregnancies in women who had previously undergone HSTC, with conditioning regimen including total body irradiation. One pregnancy is spontaneous and one after oocytes donation. RESULTS: In both pregnancies we observed relevant intrauterine growth retardation, attributable to a deficit in implantation and placentation. Ultrasound and histological data point to a defective placenta development, possibly sustained by uterine vessel damage caused by irradiation. A deeper understanding of factors influencing placentation post total body irradiation and HSCT, including the possible role of donor's sex and graft versus host disease, is pivotal to improve pregnancy outcomes in this specific population.

mRNA and Viral Vector COVID-19 Vaccines Do Not Affect Male Fertility: A Prospective Study.

PURPOSE: To assess whether mRNA and viral vector coronavirus disease 2019 (COVID-19) vaccines detrimentally affected semen parameters. MATERIALS AND METHODS: In this prospective study, we enrolled 101 men vaccinated for COVID-19 (76% received mRNA vaccines, 20% viral vector vaccines, 2% a mixed formulation, and for 2 men no information about vaccine type was available) in 2021 and with a previous semen analysis. For each man we compared semen parameters before and after vaccination. RESULTS: Post-vaccine samples were obtained at a median of 2.3±1.5 months after the second dose. After vaccination, the median sample volume significantly decreased (from 3.0 to 2.6 mL, p=0.036), whereas the median sperm concentration, the progressive motility, and total motile sperm count increased (from 25.0 to 43.0 million/mL, p<0.0001; from 50% to 56%, p=0.022; from 34.8 to 54.6 million, p<0.0001, respectively). Thirty-four patients were oligospermic before the vaccine, and also in these patients we observed a significant increase of sperm parameters after vaccine. Finally, we confirmed the aforementioned results in men who received a mRNA or a viral vector vaccine. CONCLUSIONS: The semen parameters following COVID-19 vaccination did not reflect any causative detrimental effect from vaccination, and for the first time we demonstrated that this applies to both mRNA and viral-vector vaccines. The known individual variation in semen and the reduced abstinence time before the post-vaccine sample collection may explain the increases in sperm parameters.

Hyaluronic acid-sperm selection significantly improves the clinical outcome of couples with previous ICSI cycles failure.

BACKGROUND: Beneficial effects of hyaluronic acid (HA)-based selection of spermatozoa for intracytoplasmic sperm injection (ICSI) are still controversial, and further studies are needed to categorize patients that might benefit from such a method. OBJECTIVE: We investigated whether HA sperm selection improved ICSI outcome of couples with previous ICSI cycle failure. MATERIALS AND METHODS: In this retrospective study, we prospectively collected data of (i) Group 1: 96 couples who performed one failed ICSI cycle ("1st procedure," n = 96) followed by another ICSI cycle ("2nd procedure," n = 101); ii) Group 2: 87 couples who performed one failed ICSI cycle (n = 87) followed by an HA-ICSI cycle (n = 104). Differences between procedures and groups were measured by paired and independent statistical tests, respectively. A generalized linear mixed model analyzed the effect of procedure on the outcomes and the interaction between procedures and groups. RESULTS: Injection of HA-bound sperm significantly improved cleavage rate with respect to standard ICSI (p = 0.026). No evolutive pregnancies were obtained in the 1st ICSI attempts. The 2nd ICSI cycles resulted in successfully seven pregnancies. In HA-ICSI cycles, the better quality of embryos with respect to ICSI (p = 0.034) increased the choice of day 5 embryo transfer (p = 0.030), which resulted in successfully 28 pregnancies. No differences were observed in clinical outcomes of the two ICSI procedures in Group 1, while pregnancy and implantation rates were significantly higher in HA-ICSI with respect to ICSI cycles (p = 0.001, p < 0.0001, respectively). No negative perinatal outcomes were recorded. DISCUSSION: In couples where previous 1st ICSI failed, selection of HA-bound spermatozoa significantly improved clinical outcomes with respect to further standard ICSI. CONCLUSION: This study identified couples with previous ICSI cycles failure as a category of infertile patients that really may benefit from HA sperm selection before ICSI.

Effect of Multiple Sclerosis and Its Treatments on Male Fertility: Cues for Future Research.

Multiple sclerosis is a chronic disease that may lead to different types of symptoms and disabilities. with the better quality of life and decreased disability due to early diagnosis and the availability of disease-modifying therapies (DMTs), the treating physician is increasingly asked to counsel patients on its effects on fertility and reproduction. In particular, reproductive issues are still scarcely studied and discussed in men. Among the still open questions are the following: (a) Does multiple sclerosis cause infertility per sè? (b) Is multiple sclerosis correlated with conditions that increase the risk of infertility? (c) Do DMTs or other therapies for multiple sclerosis impact gonadal function in men? The aim of this review is to provide an overview on the available literature data about the reproductive issues unique to men with multiple sclerosis, underlining the numerous areas where evidence is lacking and, therefore, the priorities for future research.