Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.

The BISTIM study: a randomized controlled trial comparing dual ovarian stimulation (duostim) with two conventional ovarian stimulations in poor ovarian responders undergoing IVF.

STUDY QUESTION: Is the total number of oocytes retrieved with dual ovarian stimulation in the same cycle (duostim) higher than with two consecutive antagonist cycles in poor responders? SUMMARY ANSWER: Based on the number of total and mature oocytes retrieved in women with poor ovarian response (POR), there is no benefit of duostim versus two consecutive antagonist cycles. WHAT IS KNOWN ALREADY: Recent studies have shown the ability to obtain oocytes with equivalent quality from the follicular and the luteal phase, and a higher number of oocytes within one cycle when using duostim. If during follicular stimulation smaller follicles are sensitized and recruited, this may increase the number of follicles selected in the consecutive luteal phase stimulation, as shown in non-randomized controlled trials (RCT). This could be particularly relevant for women with POR. STUDY DESIGN, SIZE, DURATION: This is a multicentre, open-labelled RCT, performed in four IVF centres from September 2018 to March 2021. The primary outcome was the number of oocytes retrieved over the two cycles. The primary objective was to demonstrate in women with POR that two ovarian stimulations within the same cycle (first in the follicular phase, followed by a second in the luteal phase) led to the retrieval of 1.5 (2) more oocytes than the cumulative number of oocytes from two consecutive conventional stimulations with an antagonist protocol. In a superiority hypothesis, with power 0.8 alpha-risk 0.05 and a 35% cancellation rate, 44 patients were needed in each group. Patients were randomized by computer allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eighty-eight women with POR, defined using adjusted Bologna criteria (antral follicle count ≤5 and/or anti-Müllerian hormone ≤1.2 ng/ml) were randomized, 44 in the duostim group and 44 in the conventional (control) group. HMG 300 IU/day with flexible antagonist protocol was used for ovarian stimulation, except in luteal phase stimulation of the duostim group. In the duostim group, oocytes were pooled and inseminated after the second retrieval, with a freeze-all protocol. Fresh transfers were performed in the control group, frozen embryo transfers were performed in both control and duostim groups in natural cycles. Data underwent intention-to-treat and per-protocol analyses. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference between the groups regarding demographics, ovarian reserve markers, and stimulation parameters. The mean (SD) cumulative number of oocytes retrieved from two ovarian stimulations was not statistically different between the control and duostim groups, respectively, 4.6 (3.4) and 5.0 (3.4) [mean difference (MD) [95% CI] +0.4 [-1.1; 1.9], P = 0.56]. The mean cumulative numbersof mature oocytes and total embryos obtained were not significantly different between groups. The total number of embryos transferred by patient was significantly higher in the control group 1.5 (1.1) versus the duostim group 0.9 (1.1) (P = 0.03). After two cumulative cycles, 78% of women in the control group and 53.8% in the duostim group had at least one embryo transfer (P = 0.02). There was no statistical difference in the mean number of total and mature oocytes retrieved per cycle comparing Cycle 1 versus Cycle 2, both in control and duostim groups. The time to the second oocyte retrieval was significantly longer in controls, at 2.8 (1.3) months compared to 0.3 (0.5) months in the duostim group (P < 0.001). The implantation rate was similar between groups. The cumulative live birth rate was not statistically different, comparing controls versus the duostim group, 34.1% versus 17.9%, respectively (P = 0.08). The time to transfer resulting in an ongoing pregnancy did not differ in controls 1.7 (1.5) months versus the duostim group, 3.0 (1.6) (P = 0.08). No serious adverse events were reported. LIMITATIONS, REASONS FOR CAUTION: The RCT was impacted by the coronavirus disease 2019 pandemic and the halt in IVF activities for 10 weeks. Delays were recalculated to exclude this period; however, one woman in the duostim group could not have the luteal stimulation. We also faced unexpected good ovarian responses and pregnancies after the first oocyte retrieval in both groups, with a higher incidence in the control group. However, our hypothesis was based on 1.5 more oocytes in the luteal than the follicular phase in the duostim group, and the number of patients to treat was reached in this group (N = 28). This study was only powered for cumulative number of oocytes retrieved. WIDER IMPLICATIONS OF THE FINDINGS: This is the first RCT comparing the outcome of two consecutive cycles, either in the same menstrual cycle or in two consecutive menstrual cycles. In routine practice, the benefit of duostim in patients with POR regarding fresh embryo transfer is not confirmed in this RCT: first, because this study demonstrates no improvement in the number of oocytes retrieved in the luteal phase after follicular phase stimulation, in contrast to previous non-randomized studies, and second, because the freeze-all strategy avoids a pregnancy with fresh embryo transfer after the first cycle. However, duostim appears to be safe for women. In duostim, the two consecutive processes of freezing/thawing are mandatory and increase the risk of wastage of oocytes/embryos. The only benefit of duostim is to shorten the time to a second retrieval by 2 weeks if accumulation of oocytes/embryos is needed. STUDY FUNDING/COMPETING INTERESTS: This is an investigator-initiated study supported by a research Grant from IBSA Pharma. N.M. declares grants paid to their institution from MSD (Organon France); consulting fees from MSD (Organon France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. I.A. declares honoraria from GISKIT and support for travel and meetings from GISKIT. G.P.-B. declares Consulting fees from Ferring and Merck KGaA; honoraria from Theramex, Gedeon Richter, and Ferring; payment for expert testimony from Ferring, Merck KGaA, and Gedeon Richter; and support for travel and meetings from Ferring, Theramex, and Gedeon Richter. N.C. declares grants from IBSA pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. E.D. declares support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Ferring, Gedeon Richter, Theramex, and General Electrics. C.P.-V. declares support for travel and meetings from IBSA Pharma, Merck KGaA, Ferring, Gedeon Richter, and Theramex. M.Pi. declares support for travel and meetings from Ferring, Gedeon Richetr, and Merck KGaA. M.Pa. declares honoraria from Merck KGaA, Theramex, and Gedeon Richter; support for travel and meetings from Merck KGaA, IBSA Pharma, Theramex, Ferring, Gedeon Richter, and MSD (Organon France). H.B.-G. declares honoraria from Merck KGaA, and Gedeon Richter and support for travel and meetings from Ferring, Merck KGaA, IBSA Pharma, MSD (Organon France), Theramex, and Gedeon Richter. S.G. and M.B. have nothing to declare. TRIAL REGISTRATION NUMBER: Registration number EudraCT: 2017-003223-30. ClinicalTrials.gov identifier: NCT03803228. TRIAL REGISTRATION DATE: EudraCT: 28 July 2017. ClinicalTrials.gov: 14 January 2019. DATE OF FIRST PATIENT'S ENROLMENT: 3 September 2018.

The type of SARS-CoV-2 vaccine does not affect ovarian function in assisted reproduction cycle.

OBJECTIVE: To assess whether vaccination or the type of vaccine against SARS-CoV-2 affects ovarian function in an assisted reproduction treatment. DESIGN: A retrospective and observational study. SETTING: University-affiliated private in vitro fertilization (IVF) center. PATIENT(S): Five hundred one patients who had received the complete vaccination schedule. INTERVENTION(S): Treatment before and after vaccination. MAIN OUTCOME MEASURE(S): Parameters for both reproductive outcomes and IVF results in patients vaccinated RESULT(S): We included 510 patients, distributed as follows: 13.5% (n = 69) received a viral vector vaccine, either the adenovirus serotype 26 vector vaccine (Ad26.CoV2.S; Janssen; n = 31) or the chimpanzee adenovirus vector vaccine (ChAdOx; AstraZeneca; n = 38). The remaining 86.5% (n = 441) received an messenger RNA vaccine from either Pfizer-BioNTech (n = 336) or Moderna (n = 105). Sample size for the unexposed women was n = 1190. No differences were found in any of the evaluated parameters for both reproductive outcomes and IVF results in patients vaccinated with any adenovirus or messenger RNA vaccine. When we compared the results after vaccination with different types of vaccines between the exposed and unexposed groups, and similar results were obtained in the days of stimulation or the doses of administered follicle stimulating hormone. Finally, the numbers of oocytes were as follows: Johnson & Johnson (9.2 ± 2.6), AstraZeneca (7.7 ± 1.2), Moderna (11.3 ± 1.8), Pfizer (12.6 ± 1.0), and the unvaccinated group (10.2 ± 1.5), P=0.057. CONCLUSION(S): These early results suggest no measurable detrimental effect on reproductive outcomes, regardless of the type of vaccine received.

The Development, Differentiation, and Toxicity in Reproduction.

This Special Issue is intended to provide up-to-date information on reproduction, including the reproduction of germ cells and reproductive organs (ovary, testis, and uterus) [...].

Pleiotropic Effects of IGF1 on the Oocyte.

A woman's endocrine system plays a crucial role in orchestrating cellular interactions throughout her life. The growth hormone (GH) and insulin-like growth factor (IGF) system appears to impact crucial reproductive events and cell types of the ovary, such as granulosa cells, theca cells, and oocytes. Further, IGF1 is a cornerstone during embryonic development and influences predominantly developing and pre-antral follicles. In this commentary, we will emphasize the pleiotropic effects of IGF1 on physiological processes inside the egg. Herein, we will provide a brief overview on IGF1 related cell signal transduction pathways during the maturation and aging of oocytes. We aim to elucidate from a molecular and biochemical point of view if IGF1 in women with metabolic imbalances such as obesity or diabetes could be used in clinics as a novel, reliable estimator for the developmental competence of an oocyte.

SARS-CoV-2 infection negatively affects ovarian function in ART patients.

Several organs, such as the heart, breasts, intestine, testes, and ovaries, have been reported to be target tissues of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date, no studies have demonstrated SARS-CoV-2 infection in the female reproductive system. In the present study, we investigated the effects of SARS-CoV-2 infection on ovarian function by comparing follicular fluid (FF) from control and recovered coronavirus disease 2019 (COVID-19) patients and by evaluating the influence of these FF on human endothelial and non-luteinized granulosa cell cultures. Our results showed that most FFs (91.3%) from screened post COVID-19 patients were positive for IgG antibodies against SARS-CoV-2. Additionally, patients with higher levels of IgG against SARS-CoV-2 had lower numbers of retrieved oocytes. While VEGF and IL-1ß were significantly lower in post COVID-19 FF, IL-10 did not differ from that in control FF. Moreover, in COV434 cells stimulated with FF from post COVID-19 patients, steroidogenic acute regulatory protein (StAR), estrogen-receptor ß (Erß), and vascular endothelial growth factor (VEGF) expression were significantly decreased, whereas estrogen-receptor α (ERα) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) did not change. In endothelial cells stimulated with post COVID-19 FF, we observed a decrease in cell migration without changes in protein expression of certain angiogenic factors. Both cell types showed a significantly higher γH2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that the SARS-CoV-2 infection adversely affects the follicular microenvironment, thus dysregulating ovarian function.

Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary.

OBJECTIVE: To determine the temporal expression of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2, in dominant follicles throughout the periovulatory period in women and the regulatory mechanisms underlying ACE2 expression in human granulosa/lutein cells (hGLC). DESIGN: Experimental prospective clinical study and laboratory-based investigation. SETTING: University Medical Center and private in vitro fertilization center. PATIENT(S): Thirty premenopausal women undergoing surgery for tubal ligation and 16 premenopausal women undergoing in vitro fertilization. INTERVENTION(S): Administration of human chorionic gonadotropin (hCG) and harvesting of preovulatory/ovulatory follicles by timed laparoscopy, and collection of granulosa/lutein cells and cumulus cells at the time of oocyte retrieval. MAIN OUTCOME MEASURE(S): Expression and localization of ACE2 in granulosa cells and dominant follicles collected throughout the periovulatory period of the menstrual cycle and in hGLC using quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry. RESULT(S): ACE2 expression (mRNA and protein) is up-regulated in human ovulatory follicles after administration of hCG. ACE2 expression was higher in cumulus cells than in granulosa cells. hCG increased the expression of ACE2 in primary hGLC cultures; the increase was inhibited by RU486 (an antagonist for progesterone receptor and glucocorticoid receptor) and CORT125281 (a selective glucocorticoid receptor antagonist), but not by AG1478 (an EGF receptor tyrosine kinase inhibitor) or by dexamethasone. CONCLUSION(S): The hormone-regulated expression of ACE2 in granulosa cells suggests a potential role of ACE2 in the ovulatory process. These data also imply the possible impact of COVID-19 on a vital cyclic event of ovarian function and thus on women's overall reproductive health. However, SAR-CoV-2 infection in ovarian cells in vivo or in vitro has yet to be determined.

Co-expression of the SARS-CoV-2 entry molecules ACE2 and TMPRSS2 in human ovaries: Identification of cell types and trends with age.

The high rate of SARS-CoV-2 infection poses a serious threat to public health. Previous studies have suggested that SARS-CoV-2 can infect human ovary, the core organ of the female reproductive system. However, it remains unclear which type of ovarian cells are easily infected by SARS-CoV-2 and whether ovarian infectivity differs from puberty to menopause. In this study, public datasets containing bulk and single-cell RNA-Seq data derived from ovarian tissues were analyzed to demonstrate the mRNA expression and protein distribution of the two key entry receptors for SARS-CoV-2-angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2). Furthermore, an immunohistochemical study of ACE2 and TMPRSS2 in human ovaries of different ages was conducted. Differentially expressed gene (DEG) analysis of ovaries of different ages and with varying ovarian reserves was conducted to explore the potential functions of ACE2 and TMPRSS2 in the ovary. The analysis of the public datasets indicated that the co-expression of ACE2 and TMPRSS2 was observed mostly in oocytes and partially in granulosa cells. However, no marked difference was observed in ACE2 or TMPRSS2 expression between young and old ovaries and ovaries with low and high reserves. Correspondingly, ACE2 and TMPRSS2 were detected in the human ovarian cortex and medulla, especially in oocytes of different stages, with no observed variations in their expression level in ovaries of different ages, which was consistent with the results of bioinformatic analyses. Remarkably, DEG analysis showed that a series of viral infection-related pathways were more enriched in ACE2-positive ovarian cells than in ACE2-negative ovarian cells, suggesting that SARS-CoV-2 may potentially target specific ovarian cells and affect ovarian function. However, further fundamental and clinical research is still needed to monitor the process of SARS-CoV-2 entry into ovarian cells and the long-term effects of SARS-CoV-2 infection on the ovarian function in recovered females.

Vaspin, a novel adipokine in woman granulosa cells physiology and PCOS pathogenesis?

Vaspin is a novel adipokine mainly expressed in visceral adipose tissue and closely related to obesity and insulin-resistance. Currently, data about its ovarian expression are limited to animal models and its role in human reproduction is largely unexplored. Our study's aims were then to characterise vaspin expression in the human ovary and to study in vitro its effects on granulosa cells physiology. Secondly, we assessed vaspin and its receptor GRP78 variations in granulosa cells and follicular fluid of a cohort of 112 infertile women undergoing an in vitro fertilisation procedure and allocated to three groups, each including normal-weight and obese subjects: 34 PCOS patients, 33 women with isolated polycystic ovary morphology (ECHO group) and 45 controls. Vaspin and GRP78 expression in the ovary was assessed by immunohistochemistry, RT-qPCR and Western blot. Granulosa cells and follicular fluid were analysed by RT-qPCR and ELISA, respectively. In vitro, granulosa cells metabolism was studied after stimulation with recombinant human vaspin, with and without a siRNA directed against GRP78. Vaspin was highly expressed in the human ovary and concentration-dependently enhanced granulosa cells steroidogenesis, proliferation and viability through GRP78 (P < 0.0001). Vaspin levels in both granulosa cells and follicular fluid were significantly higher in obese women (P < 0.0001) and in the normal-weight ECHO group (P < 0.001), which also had the highest expression rates of GRP78 (P < 0.05). Although further investigation is needed, vaspin appears as a novel modulator of human granulosa cells physiology and possibly plays a role in PCOS pathogenesis, notably protecting from insulin-resistance induced complications.

Ovarian vein thrombosis in the postnatal period.

Although ovarian vein thrombosis (OVT) is classically considered a puerperal pathology, it can also occur in nonpuerperal settings such as endometritis, pelvic inflammatory disease, Crohn's disease, pelvic or gynaecological surgeries and thrombophilia. Hypercoagulation conditions such as antiphospholipid syndrome, systemic lupus erythematosus, factor V Leiden and protein C and S deficiency are all recognised risk factors. It is also a known complication during pregnancy often presenting with fever and lower abdominal pain within weeks after delivery. Its incidence is exceedingly rare, occurring in 0.05% of all pregnancies that result in live births and peaking around 2-6 days after delivery. Its preferential involvement of the right ovarian vein may be explained by the compression of the inferior vena cava and the right ovarian vein due to dextrorotation of the uterus during pregnancy. Furthermore, antegrade flow of blood and multiple incompetent valves in the right ovarian vein favours bacterial infection. Complications may include sepsis and thrombus extension to the inferior vena cava or left renal vein and rarely, pulmonary embolism. The authors present the case of a 27-year-old woman with lower abdominal pain 5 weeks after an elective caesarean section. Although the diagnosis of postpartum endometritis was initially considered, a CT suggested a right OVT. She commenced treatment with low-molecular weight heparin. A high index of clinical suspicion is required in order to establish the diagnosis of this rare cause of abdominal pain, which can mimic an acute abdomen.

Ovarian vein thrombosis after coronavirus disease (COVID-19) mimicking acute abdomen: two case reports.

Coronavirus is a source of deep venous thrombosis (DVT) due to complications such as over-coagulation, blood stasis, and endothelial damage. Ovarian vein thrombosis (OVT) is a very serious and rare disease. In this study, we report tow rare case of women with coronavirus who were hospitalized with a right ovarian vein thrombosis mimicking acute abdomen who progressed well on anticoagulation. Our report adds further document in Side effects and rare localisation of obstruction of veins and arteries in patient with corona virus.

Diagnosis and resection of a giant ovarian cyst presenting in a young patient with contralateral back pain and lower limb deep vein thrombosis.

We present a case of a giant ovarian cyst in a 20-year-old woman who presented atypically at our Emergency Department with left-sided back pain followed by acute left leg swelling. Blood tests showed significantly raised C-Reactive Protein and D-Dimer. CT-Abdomen-Pelvis demonstrated a large mass in the region of the right ovary with suspicious heterogeneous filling defects in the left external iliac vein, confirmed as a left-sided deep-vein thrombosis on ultrasound Doppler. MRI revealed the lesion to be cystic and the deep venous thrombosis was treated with twice-daily Clexane. Prior to removal of the cyst, an Inferior Vena Cava Filter was placed to reduce thromboembolic risk. The cyst was resected without complication and the postoperative period was uneventful. This case occurred while face-to-face services were limited by COVID-19 and illustrates the need for robust systemic measures to safeguard patients against the emergency sequelae of insidious gynaecological pathology.

Histopathological changes in Oreochromis mossambicus (Peters, 1852) ovaries after a chronic exposure to a mixture of the HIV drug nevirapine and the antibiotics sulfamethoxazole and trimethoprim.

The burden of the human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) infection has transformed the African continent into a major consumer of antiretrovirals (ARVs) drugs. In addition to HIV burden, the African continent has also a high incidence of tuberculosis (TB) and has been experiencing recurring outbreaks of several other viral, bacterial, and parasitic epidemic diseases. The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2 or Covid-19) pandemic outbreak is adding to the continent's infectious diseases burden as experts are predicting that it will be here for a long time. One of the consequences of these infectious diseases is that antiviral and antibiotic compounds have become some of the most consumed pharmaceuticals on the continent. Many of these drugs have been frequently detected in surface waters across Africa. There is limited information available on the adverse effects of the mixtures of different types of pharmaceuticals in African aquatic environments on fish reproduction. The present study investigated the effects of the ARV drug nevirapine (NVP - 1.48 and 3.74 µg/L) and its mixture with the antibiotic sulfamethoxazole (3.68 µg/L) and trimethoprim (0.87 µg/L) on O. mossambicus gonads using histopathological endpoints as biomarkers. The fish (n = 52) were exposed for 30 days in a static renewal system. Female O. mossambicus exposed to nevirapine (3.74 µg/L) and to NVP - antibiotic mixture recorded higher ovary indices. Statistically significant differences were found in female ovary indices between the fish exposed to NVP (3.74 µg/L) and the control fish (p = 0.002) as well as between the fish exposed to the NVP - antibiotic mixture and the control fish (p = 0.009). The main observed histopathological changes in the ovaries were increased vitellogenic oocyte atresia and vacuolation of the interstitial tissue in the fish exposed to NVP - antibiotic mixture. It is evident that the presence of NVP - antibiotics mixture in water triggered the observed histopathology in female fish ovaries. The detected abnormal high rate of atretic oocytes could result in impaired fish reproduction.

Female reproductive tract has low concentration of SARS-CoV2 receptors.

There has been significant concern regarding fertility and reproductive outcomes during the SARS-CoV2 pandemic. Recent data suggests a high concentration of SARS-Cov2 receptors, ACE2 or TMPRSS2, in nasal epithelium and cornea, which explains person-to-person transmission. We investigated the prevalence of SARS-CoV2 receptors among reproductive tissues by exploring the single-cell sequencing datasets from uterus, myometrium, ovary, fallopian tube, and breast epithelium. We did not detect significant expression of either ACE2 or TMPRSS2 in the normal human myometrium, uterus, ovaries, fallopian tube, or breast. Furthermore, none of the cell types in the female reproductive organs we investigated, showed the co-expression of ACE2 with proteases, TMPRSS2, Cathepsin B (CTSB), and Cathepsin L (CTSL) known to facilitate the entry of SARS2-CoV2 into the host cell. These results suggest that myometrium, uterus, ovaries, fallopian tube, and breast are unlikely to be susceptible to infection by SARS-CoV2.

Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age.

RESEARCH QUESTION: Does SARS-CoV-2 infection have an effect on ovarian reserve, sex hormones and menstruation of women of child-bearing age? DESIGN: This is a retrospective, cross-sectional study in which clinical and laboratory data from 237 women of child-bearing age diagnosed with COVID-19 were retrospectively reviewed. Menstrual data from 177 patients were analysed. Blood samples from the early follicular phase were tested for sex hormones and anti-Müllerian hormone (AMH). RESULTS: Among 237 patients with confirmed COVID-19, severely ill patients had more comorbidities than mildly ill patients (34% versus 8%), particularly for patients with diabetes, hepatic disease and malignant tumours. Of 177 patients with menstrual records, 45 (25%) patients presented with menstrual volume changes, and 50 (28%) patients had menstrual cycle changes, mainly a decreased volume (20%) and a prolonged cycle (19%). The average sex hormone and AMH concentrations of women of child-bearing age with COVID-19 were not different from those of age-matched controls. CONCLUSIONS: Average sex hormone concentrations and ovarian reserve did not change significantly in COVID-19 women of child-bearing age. Nearly one-fifth of patients exhibited a menstrual volume decrease or cycle prolongation. The menstruation changes of these patients might be the consequence of transient sex hormone changes caused by suppression of ovarian function that quickly resume after recovery.

Effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on reproductive system.

Since the emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in December 2019, it has rapidly spread across many countries and it has become a crucial global health concern. Furthermore, SARS-CoV-2 infection not only effect on respiratory system, but on reproductive system of human. However, there has been not any review described the transmission paths and effects of SARS-CoV-2 infection on human reproductive system, systematically. In order to describe the transmission paths of SARS-CoV-2, effect on the male/female reproductive system of SARS-CoV-2 and some successful prevention measures. We would like to review effect of SARS-CoV-2 on reproductive system. To conclude, SARS-CoV-2 infection might damage to male reproductive system via ACE2 receptor mediating and male patients were reportedly slightly more affected than women by SARS-CoV-2 infections.

Coronavirus Disease 2019 (SARS-CoV-2) and polycystic ovarian disease: Is there a higher risk for these women?

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with acute respiratory distress syndrome and infected patients have a relatively high risk of death. Emerging risk factors for poor outcome in this disease include age, male gender, cardiovascular co-morbidities including hypertension, prior cardiovascular disease, diabetes and more recently obesity. To date there are no data relating to SARS-CoV-2 in PCOS women. The present Clinical Opinion represents a summary of the epidemiological evidence and possible pathophysiological mechanisms regarding PCOS and COVID-19. PCOS women could be more susceptible to infections compared to non-PCOS women. Insulin resistance and the associated hyperinsulinaemia are drivers for enhanced steroidogenesis in women with PCOS. Weight-gain and obesity, through their worsening effects on insulin resistance, thereby drive enhanced steroidogenesis and hyperandrogenism. All these features represent key points to provide an explanation for the possible association between PCOS and SARS-CoV-2. Indeed, androgens may drive clinical results in COVID-19, through the expression of TMPRSS2, a cellular co-receptor necessary for SARS-CoV-2 infection and through androgen-mediated immune modulation. In women with PCOS the endocrine-immune axis leads to immune dysfunction with a state of chronic inflammation, and hyperandrogenism and IR with compensatory hyperglycaemia could play a determining role in the pathophysiogenesis of the infection. However, it is possible that only specific PCOS phenotypes may be more susceptible. In addition, vitamin D deficiency and gut dysbiosis are another important factor potentially involved in the increased risk of developing severe forms of COVID-19 in PCOS women. Further scientific investigations are needed with the aim of understanding which women are most at risk of becoming infected or developing complications, what are the causal mechanisms on which it is possible to intervene with prophylactic and therapeutic measures and what the long-term consequences will be on the health of these patients.

Left gonadal vein thrombosis in a patient with COVID-19-associated coagulopathy.

COVID-19 disease is a viral illness that predominantly causes pneumonia and severe acute respiratory distress syndrome. The endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism. The exact mechanism of hypercoagulability is still under investigation, but it is known to be associated with poor prognosis. The most common thrombotic complication reported among these patients is pulmonary embolism. To our knowledge, gonadal vein thrombosis is an uncommon phenomenon that has not been reported in the setting of COVID-19-associated coagulopathy. We report an unusual case of ovarian vein thrombosis and pulmonary embolism associated with COVID-19 presenting with abdominal pain. To our knowledge, this is the first reported case of COVID-19 with absent respiratory symptoms and presentation with venous thrombosis in an unusual location.