Comparison of ICSI and Conventional IVF in Non-Male Factor Patients with Less Than Four Oocytes

Background: We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) in order to clarify if lower number of oocytes is a drawback for proceeding to C-IVFMaterials and methods: In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤3 cumulus-oocyte-complexes available for fertilisation were analysed. Exclusion criteria were: woman age>42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1,n=77); ICSI non-male factor (Group 2, n=65); ICSI male factor- ICSI/MF n=49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. Results: Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85,68%, 72,58%, 73,33% respectively, p=0,004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20,42%, 28,49%, 23,33% respectively, p=0,407) and live birth rates (26,8%, 30,6%, 31,1% respectively, p=0.643).Conclusions: In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient’s previous history regardless of the ovarian reserve.

The Impact of Oxidative Stress in Male Infertility

At present infertility is affecting about 15% of couples and male factor is responsible for almost 50% of infertility cases. Oxidative stress, due to enhanced Reactive Oxygen Species (ROS) production and/or decreased antioxidants, has been repeatedly suggested as a new emerging causative factor of this condition. However, the central roles exerted by ROS in sperm physiology cannot be neglected. On these bases, the present review is focused on illustrating both the role of ROS in male infertility and their main sources of production. Oxidative stress assessment, the clinical use of redox biomarkers and the treatment of oxidative stress-related male infertility are also discussed.

Does Prevalence of Sexual Dysfunction Differ Among the Most Common Causes of Infertility? A Cross-Sectional Study

Background Sexuality as a fundamental component of women’s health, can be affected by infertility. The current study aimed at comparing the prevalence of sexual dysfunction among women with the most common causes of infertility. Methods The current cross-sectional study was conducted on 240 infertile females with infertility due to polycystic ovary syndrome (PCOS, n=80), endometriosis (n=80) and male factor (n=80) at Royan Institute for Reproductive Biomedicine (Tehran, Iran) and 160 fertile women at health care centers, between May 2016 and June 2017. Sexual function was assessed by Female Sexual Function Index (FSFI). Data were analyzed using SPSS (version 25.00) and differences were regarded statistically significant at p < 0. 05. Results The prevalence of female sexual dysfunction was 98.8% in women with PCOS, 100.0% in those with endometriosis, and 80.0% in those with male factor infertility. Overall, 36.2% of the enrolled fertile women were suffering from sexual dysfunction. Conclusions There was an association between the prevalence of female sexual dysfunction or individual domain scores of the FSFI, and infertility etiologies. Therefore, infertility care providers are required to take this into consideration and develop preventive strategies in this regard.

Randomized allocation of oocytes to IVF or ICSI for IVF-naïve cases with unexplained infertility in an IVF-ICSI Split protocol favors ICSI to optimize live birth outcomes

In assisted reproduction treatments (ART), applying the ICSI method for fertilization of oocytes rather than traditional IVF method, is regarded as controversial for two reasons, namely utility and safety. Our study examines an IVF-ICSI Split model for couples with unexplained infertility, where male factor is meticulously excluded and ART is conducted by a strict algorithm, a commitment to blastocyst culture, along with single embryo transfers and a high commitment to cryopreservation. From 242 treatment cycles, 3346 oocytes recovered (13.8 per OPU) were randomly allocated to IVF or ICSI and the fertilization rates standardized to the number of 2PNS arising from each group applying the metaphase II oocyte number identified for the ICSI group, as the denominator for both groups. The fertilization rates were significantly higher overall for ICSI (83.2% vs 65.4%; p<0.0001), being most pronounced for women under 40 years. The resultant embryos had equivalent implantation rates in both fresh ET and frozen (FET) cycles with no significant differences in pregnancy rates, miscarriage rates or live birth outcomes indicating equivalent embryo quality. However, there were significantly higher numbers of ICSI-generated embryos cryopreserved and subsequent FET procedures showed higher live birth rates (21 births vs 6 births; p<0.005) and potential livebirths (214 births vs 104 births; p<0.0001). No congenital fetal abnormalities were detected in any of the 199 babies delivered during the study period to December 2020, neither IVF-generated nor ICSI-generated. Whilst the data strongly favors ICSI, there were 2 women (from 26 with fertilization in one arm only) who demonstrated fertilization only in the IVF arm of the study. We conclude that the IVF-ICSI Split model should be undertaken on all IVF-naïve women with unexplained infertility to determine the appropriate fertilization mode, albeit ICSI will be safely preferred for >90% of cases.

Toxicity of Antioxidant Supplements in Patients with Male Factor Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Treating oxidative stress through antioxidant therapy has been considered an appealing strategy in the management of male infertility. However, evidence regarding the toxicity of antioxidant therapy is controversial. We summarized the available clinical evidence on the toxicity associated with the use of antioxidants in infertile males. A systematic review was performed in March 2021. We included randomized controlled trials evaluating the incidence of adverse events in male patients with infertility receiving antioxidant therapy. Thirteen studies involving 1999 male patients were identified. Antioxidant supplementation in patients with male factor infertility was associated with a statistically significantly increased risk of nausea (Odds Ratio: 2.16, 95% Confidence Interval: 1.05–4.43, p = 0.036), headache (Odds Ratio: 3.05, 95% Confidence Interval: 1.59– 5.85 p = 0.001), and dyspepsia (Odds Ratio: 4.12, 95% Confidence Interval: 1.43–11.85, p = 0.009) compared to a placebo. Treatment discontinuation due to adverse events was not significantly higher in patients taking antioxidants compared to a placebo (Odds Ratio: 2.29, 95% Confidence Interval: 0.76–6.88, p = 0.139). When antioxidant supplementation is considered, a more accurate risk/benefit analysis is warranted.

Relationship between pregnancy rate and number of intrauterine insemination cycles during the study of comparative efficacy of letrozole and clomiphene citrate adjuvants to gonadotropin stimulation in controlled ovarian stimulation cycles combined with intrauterine insemination therapy

Background: Infertility is commonly defined as the failure of conception after at least twelve months of unprotected intercourse. Factors contributing are both male and female in which unexplained etiology accounts for 51%, male factor 28%, endometriosis 17% and ovulatory disorders 4%.Methods: Prospective, randomized study was conducted at DRRPG medical college, Tanda, Kangra, Himachal Pradesh. In our study, patients were randomized into two groups of 30 each. Women in group A received clomiphene citrate 100mg/day and group B received letrozole 2.5 mg/day from day 3-7 of menstrual cycle. All the patients received human menopausal gonadotropin 75 U given every alternate day from day 5 until HCG administration. Ovulation was triggered with recombinant HCG (5000 IUIM) when the dominant follicles reached 18 mm in diameter. A single IUI was performed 36 hours later. A maximum of four cycles were given.Results: In our study, total number of induction cycles given in group A and B were 120 and 114 respectively. Out of these, 112 and 111 IUI cycles were done in group A and B respectively. A pregnancy rate of 1.66% and 7.87% per IUI cycle was observed in group A and B respectively.Thus it is concluded that the pregnancy rates were significantly higher in letrozole group (30%) in comparison to clomiphene citrate group (6.66%).Conclusions: Aromatase inhibitor letrozole appears to constitute a good alternative to clomiphene citrate in patients with unexplained infertility undergoing gonadotropin-stimulated COS cycles combined with IUI therapy.

Endocrinopathies and Male Infertility

Male infertility is approaching a concerning prevalence worldwide, and inflicts various impacts on the affected couple. The hormonal assessment is a vital component of male fertility evaluation as endocrine disorders are markedly reversible causatives of male infertility. Precise hormonal regulations are prerequisites to maintain normal male fertility parameters. The core male reproductive event, spermatogenesis, entails adequate testosterone concentration, which is produced via steroidogenesis in the Leydig cells. Physiological levels of both the gonadotropins are needed to achieve normal testicular functions. The hypothalamus-derived gonadotropin-releasing hormone (GnRH) is considered the supreme inducer of the gonadotropins and thereby the subsequent endocrine reproductive events. This hypothalamic–pituitary–gonadal (HPG) axis may be modulated by the thyroidal or adrenal axis and numerous other reproductive and nonreproductive hormones. Disruption of this fine hormonal balance and their crosstalk leads to a spectrum of endocrinopathies, inducing subfertility or infertility in men. This review article will discuss the most essential endocrinopathies associated with male factor infertility to aid precise understanding of the endocrine disruptions-mediated male infertility to encourage further research to reveal the detailed etiology of male infertility and perhaps to develop more customized therapies for endocrinopathy-induced male infertility.

Male factor of infertility in spinal cord injury

Currently, traumatic spinal cord injury disease is a common problem in men of sexual and reproductive active age. The result may be disturbance of erectile and ejaculatory functions, which often leads to inability of natural conception. Vibrostimulation, electrical stimulation or surgical sperm extraction, intrauterine insemination procedures and assisted reproductive technologies are the standard procedures in the treatment of fertility disorders in men with spinal cord injury and dysejaculation. The effectiveness of the techniques directly depends on the quality of sperm and the female reproductive health. Currently, the potential mechanisms of the disorders of spermatogenesis in patients with spinal cord injury are not clearly learned. The literature review of sexual dysfunction and pathogenetic aspects of pathospermia in men with spinal cord injury is provided.

Two modified natural in vitro fertilisation (IVF) protocols compared to conventional IVF treatment: Retrospective data from one Danish Fertility Centre

Aim of study: Over the last decade, laboratory procedures in in vitro fertilisation (IVF) have improved. Hyperstimulated ovaries cause an overload of surplus embryos. The present study was designed to evaluate the efficiency of two different modified IVF cycle protocols trying to reduce the load of medication used for IVF: simple IVF (S-IVF), Tamoxifen 40 mg daily from day 2 in the cycle to ovulation induction) and mild IVF (M-IVF), Tamoxifen 40 mg daily and every secondary 150 IU Gonal F until ovulation induction. The study aims to evaluate their efficiency compared with our conventional IVF (C-IVF) using a short antagonist protocol. Methods: A retrospective cohort study including all patients admitted to IVF for unexplained infertility, tubal factor, and male factor. In all stimulated cycles patients aimed at having fresh embryos transferred and surplus good embryos cryopreserved. All patients were recruited in the same period and allocated to the different treatments on their own request. The study was conducted between June 2019 and February 2021. Results: In total the study included 976 IVF cycles. 651 cycles from C-IVF, 145 cycles from S-IVF and 180 cycles from M-IVF. Mean age in the groups were comparable. Mean number of eggs retrieved was 6.1 (C-IVF), 1.2 (S-IVF) and 3.0 (M-IVF). Pregnancy rate per fresh transfer was found to be 29% for C-IVF, 26% in the S-IVF group and for the M-IVF 20%. Conclusion: Modified IVF stimulation protocols may be an important step towards a simpler assisted reproductive technology (ART) approach. More tolerable for women, easier and cheaper for patients and society they maintain acceptable clinical pregnancy rates. Large prospective studies need to be performed in the future.

Association between clinical and IVF laboratory parameters and miscarriage after single euploid embryo transfers

Background The goal of this study was to investigate which factors, excluding embryo aneuploidies, are associated with miscarriage in patients who have undergone a single euploid blastocyst transfer. Methods Retrospective, observational and multicenter study with 2832 patients undergoing preimplantational genetic testing for aneuploidies (PGT-A) due to repeated implantation failure, recurrent pregnancy loss, advanced maternal age or severe male factor were transferred one single euploid embryo. Results One of the main findings was a significant relationship between body mass index (BMI) and miscarriage rates (13.4% in underweight women, 12.1% in normal weight, 14.5% in overweight, and 19.2% in obese women, odds ratio [OD] 1.04; 95% confidence interval [CI], 1.01–1.07 p = 0.006). Endometrial thickness (OD 0.65; 95%, 0.52–0.77 p = 0.04) and type of endometrial preparation (natural cycle or hormone replacement cycle) (OD 0.77; 95%, 0.52–0.77, p = 0.04) were also associated with miscarriage rates. Conclusions BMI was strongly associated to miscarriage rates. We also observed a weaker association with endometrial thickness and with the type of endometrial preparation (natural cycle or hormone replacement cycle). None of the other studied variables (biopsy day, maternal and male age, duration of infertility, cycle length, previous miscarriages, previous live births, previous In Vitro Fertilization (IVF) cycles, endometrial pattern and/or diagnosis) were associated with miscarriage rates.