The Effects of SARS-CoV-2 Infection on Female Fertility: A Review of the Literature

As the coronavirus pandemic is far from ending, more questions regarding the female reproductive system, particularly fertility issues, arise. The purpose of this paper is to bring light upon the possible link between COVID-19 and women’s reproductive health. This review emphasizes the effect of SARS-CoV-2 on the hormones, endometrium and menstrual cycle, ovarian reserve, follicular fluid, oocytes, and embryos. The results showed that endometrial samples did not express SARS-CoV-2 RNA. Regarding the menstrual cycle, there is a large range of alterations, but they were all reversible within the following months. The ovarian reserve was not significantly affected in patients recovering from both mild and severe infection in most cases, except one, where the levels of AMH were significantly lower and basal follicle-stimulating hormone (FSH) levels were increased. All COVID-19 recovered patients had positive levels of SARS-CoV-2 IgG in the follicular fluid. The amount of retrieved and mature oocytes and the fertilization rate were unharmed in three studies, except for one study, where the quantity of retrieved and mature oocytes was reduced in patients with higher levels of SARS-CoV-2 antibodies. The numbers of blastocysts, top-quality embryos, and euploid embryos were affected in most of the studies reviewed.

Comparative advantage of anti-Mullerian hormone over other ovarian reserve metric (basal hormonal test) in prediction of fertility in women with varying menstrual cycle

Objective: Anti-Mullerian hormone has been indicated as a novel biomarker for ovarian reserve assessment. This study aimed to determine the comparative advantage of serum levels of AMH, FSH, LH, E2, and LH/FSH ratio among women with varying menstrual cycles and duration of menstruation. Material and Method: A total of 90 subjects, which consisted of sixty subjects and thirty healthy subjects as control, were recruited. Blood samples were collected on day 3 of the menstrual cycle and evaluated for ovarian markers using the ELISA technique. All data were analyzed using SPSS version 23.0. Results: AMH and LH/FSH levels were lower in women with varying menstrual cycles than in the control group. FSH, LH, and E2 levels were significantly higher in women with varying menstrual cycles and flow duration than in the control group(P<0.05). AMH was negatively correlated with age (r= -0.72), BMI( r= -0.4), FSH(r= - 0.3), LH(r = -0.2) (p<0.05) and E2(r= -0.2, p>0.05). Also age was positively correlated with FSH(r=0.5,p<0.05), E2(r=0.3, p<0.05) and BMI(r=0.4, p<0.05). The level of AMH was not significant with cycle length and days of flow(p>0.05). This implies that AMH can be measured independently of the cycle phase. This show that AMH was lower in women with varying menstrual cycle with an increase in gonadotrophin and E2. The strong negative relationship between age and AMH implies that age is determining factor of ovarian reserve. Conclusion: AMH combined with age and FSH may improve ovarian reserve evaluation, making AMH a better marker

Effect of autologous platelet rich plasma on anti-mullerian hormone and antral follicle count in sub fertile women with poor ovarian reserve

Background: Ovarian aging may be reversible. Platelet rich plasma (PRP) has growth factors that promote cellular proliferation and folliculogenesis. Recently published studies and case reports suggest that ovarian rejuvenation can be done by PRP treatment. The objective of the study was to evaluate the effect of platelet rich plasma on ovarian reserve markers such as anti mullerian hormone (AMH) and antral follicle count (AFC) in sub fertile women with poor ovarian reserve (POR).Methods: The self-controlled quasi experimental study was carried out on 29 sub fertile women with poor ovarian reserve. They were selected for laparoscopic tubo-peritoneal evaluation as they could not afford in vitro fertilization. During laparoscopy, 5 ml of pre prepared autologous PRP was injected into each ovary. Post-PRP AMH and AFC were measured at every cycle for a period of at least three (3) months and compared with base line values.Results: Mean age of participants was 35.9±3.2 years. Baseline AMH was 0.31±0.17 ng/ml and baseline AFC was 3.41±0.73. AMH was raised on first, second and third cycle from base line values in 58.62%, 86.21% and 91.30% of the study population respectively. AMH changes in all three cycle were statistically significant. Pregnancy occurred in three (10.34%) women during the study period.Conclusions: The injection of autologous PRP into human ovaries is a safe procedure to improve ovarian reserve markers (AMH and AFC) in women with POR.

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

Background Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here, we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently, we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. Results Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. Conclusions SRD5A1/5α reductase-1 responds epigenetically to the environment and its downregulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs.

Effect of 3 Months Exercise on Ovarian Reserve and Ovulatory Status of Premenopausal Students of Nnamdi Azikiwe University, Nnewi Campus

There is a traditional believe that if premenopausal women engage in prolonged physical exercise, they are likely to have infertility. This study assessed the effect of prolonged moderate – vigorous exercise on ovarian reserve and ovulatory status in premenopausal students of Nnamdi Azikiwe University, Nnewi Campus. The objectives were to determine the effect of moderate – vigorous intensity exercise on Anti-Mullerian hormone (AMH), day 3 Follicle stimulating hormone (FSH), Luteinizing Hormone (LH), day 3 Estrogen, day 21 Estrogen, and day 21 Progesterone levels in premenopausal women. This was a prospective comparative study involving 80 participants aged between 19 and 25 years, randomly selected and assigned to exercise group and control group. The exercise group comprised 40 participants who engaged in moderate – vigorous intensity exercise using elliptical bike for 30 minutes, five days a week for 3 months; however, 30 individuals completed the exercise. The control group comprised of 40 individuals that did not do exercise but 30 individuals completed the study. Blood (8ml) was collected from each of the participants at baseline, 1 month, 2 months, and 3 months. AMH, FSH, LH, Estrogen and Progesterone levels were analyzed using enzyme- linked Immunosorbent assay (ELISA) method. Results were regarded as significant at p˂ 0.05. In the exercise group, the serum level of day 3 FSH, LH, Estrogen were significantly lower from 7.27±0.77 mIU/ml, 7.00±0.77 mIU/ml, 36.33±5.13 pg/ml respectively at baseline to 5.62±0.48 mIU/ml, 5.36±0.80 mIU/ml, 21.36±4.34 pg/ml respectively after 3 months of exercise while there was significantly higher levels of AMH and day 21 progesterone after 3 months of exercise compared with the baseline and respective control (p<0.05). Prolonged Moderate-to-vigorous exercise may enhance fertility and well-being of premenopausal women. Key words: Anti-Mullerian hormone (AMH), day 3 Follicle stimulating hormone (FSH), Luteinizing Hormone (LH), day 3 Estrogen, day 21 Estrogen, day 21 Progesterone, moderate – vigorous exercise, ovarian reserve, ovulatory status, premenopausal women.