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.
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.
Study question Is long-acting GnRH agonist (GnRHa) trigger an efficacious and safe option in oocyte cryopreservation cycles before chemotherapy, when ovarian suppression is planned? Summary answer The flare-up effect of long-acting GnRHa is able to induce the final oocytes’ maturation and subsequently suppress ovarian function for chemotherapy What is known already When both oocyte cryopreservation and gonadal suppression during chemotherapy with long-acting GnRHa are accepted by the patient for fertility preservation (FP), the first injection of GnRHa is administered few days after oocyte retrieval in order to start oncological therapies as soon as possible. Some cases of ovarian hyperstimulation (OHSS) have been described in this setting, as a consequence of the initial flare-up effect on recently stimulated ovaries. The subsequent risks (including a possible delay in the start of chemotherapy) may discourage physicians from proposing gonadal suppression in combination with oocyte cryopreservation, denying women a FP opportunity with proven efficacy. Study design, size, duration Prospectively collected data from 75 oncological patients who underwent ovarian stimulation for oocyte cryopreservation from 2016 to 2021 were evaluated. From 2020 all patients for whom ovarian suppression after cryopreservation was planned were offered long-acting GnRHa trigger. All other patients were enrolled as controls, stratified for triggering method used (highly purified Chorionic Gonadotrophin 10000 UI or short acting GnRHa 0.2 mg). Participants/materials, setting, methods All the ovarian stimulation cycles for oocyte cryopreservation in oncological patients before chemotherapy were performed in a single tertiary level public fertility centre. Cycle outcomes were evaluated accordingly to the trigger method. Maturation rate was defined as number of cryopreserved mature oocytes/total number of oocytes retrieved. Results were compared by Mann-Whitney U test or Chi-Square test, as appropriate. When the long-acting GnRHa was used for triggering, luteal phase hormones were assessed. Main results and the role of chance After controlled ovarian stimulation (COS) with standard or random start antagonist protocol, 13 women received the long-acting GnRHa trigger (Triptorelin 3.75 mg. Group A) 36 hours before oocyte retrieval, 37 women received highly purified Chorionic Gonadotrophin 10000 UI (Group B) and 25 women the short-acting GnRHa (Triptorelin 0.2 mg. Group C). The groups were comparable in terms of demographic and clinical parameters. Median number of mature cryopreserved oocytes in group A was 11 (range 7-18) with a maturation rate of 80% (68-100), 9 (0-24) with a maturation rate of 78% (43-100) in group B, and 12 (0-34), 79% (50-100) in group C (no statistically significative difference). There was no case of OHSS in Group A. One patient in group B and one in group C developed OHSS after administration of long-acting GnRH in the luteal phase after COS (five days after oocytes retrieval). Five days after oocyte retrieval (7 days after trigger), serum FSH median level in group A was 1.29 mUI/ml (0.48-2.50) and LH median level was 1.04 mUI/ml (0.26-2.46). Limitations, reasons for caution We are aware that our data should be confirmed by more robust randomized studies and higher numbers. Wider implications of the findings We report for the first time the efficacy of long-acting GnRHa in obtaining mature oocytes and in guaranteeing complete suppression by chemotherapy initiation. The feasibility of this strategy is an important step in reducing the risk of OHSS, giving the opportunity to combine oocyte cryopreservation and ovarian suppression during chemotherapy. Trial registration number not applicable
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