The Effect of Hormonal Treatment on Ovarian Endometriomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effect of hormonal suppression of endometriosis on the size of endometriotic ovarian cysts. DATA SOURCES: The authors searched MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov from January 2012 to December 2022. METHODS OF STUDY SELECTION: We included studies of premenopausal women undergoing hormonal treatment of endometriosis for ≥3 months. The authors excluded studies involving surgical intervention in the follow-up period and those using hormones to prevent endometrioma recurrence after endometriosis surgery. Risk of bias was assessed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool. The protocol was registered in PROSPERO (CRD42022385612). TABULATION, INTEGRATION, AND RESULTS: The primary outcome was the mean change in endometrioma volume, expressed as a percentage, from baseline to at least 6 months. Secondary outcomes were the change in volume at 3 months and analyses by class of hormonal therapy. The authors included 16 studies (15 cohort studies, 1 randomized controlled trial) of 888 patients treated with dienogest (7 studies), other progestins (4), combined hormonal contraceptives (2), and other suppressive therapy (3). Globally, the decrease in endometrioma volume became statistically significant at 6 months with a mean reduction of 55% (95% confidence interval, -40 to -71; 18 treatment groups; 730 patients; p <.001; I2 = 96%). The reduction was the greatest with dienogest and norethindrone acetate plus letrozole, followed by relugolix and leuprolide acetate. The volume reduction was not statistically significant with combined hormonal contraceptives or other progestins. There was high heterogeneity, and studies were at risk of selection bias. CONCLUSION: Hormonal suppression can substantially reduce endometrioma size, but there is uncertainty in the exact reduction patients may experience.

SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients.

BACKGROUND: Short- and long-term implications of SARS-CoV-2 on the quality of the sperm and the results of this on fertility remain largely unknown due to lack of longitudinal studies. In this longitudinal observational cohort study, we aimed to analyse the differential effect and the impact of SARS-CoV-2 infection on different semen quality parameters. METHODS: Sperm quality was assessed using the World Health Organization criteria, DNA damage to sperm cells by quantifying the DNA fragmentation index (DFI) and the high-density stainability (HDS), IgA- and IgG-anti-sperm antibodies (ASA) were assessed with light microscopy. FINDINGS: SARS-CoV-2 infection was associated with sperm parameters that were independent of spermatogenic cycle like progressive motility, morphology, DFI and HDS, as well as spermatogenic cycle dependent parameters such as sperm concentration. Detection of IgA- and IgG-ASA allowed classification of patients in three different groups according to its sequence of appearance in sperm during post-COVID-19 follow-up. The maximum progressive motility was lowest during follow-up in patients without ASA (41.9%), intermediate in patients with only IgA-ASA (46.2%) and highest inpatients who had both IgA- and IgG-ASA (54.9%). INTERPRETATION: SARS-CoV-2 infection was associated with changes of all analysed sperm parameters to a different degree which is also observed in their return to normality and is suggestive of individual variations in the patient's immune system performance. Firstly, sperm production is decreased through temporal immune mediated arrest of active meiosis, and secondly immune induced sperm DNA damage prevents fertilization if transferred to the oocyte. Both mechanisms are temporal, and most sperm parameters return to baseline after infection. FUNDING: AML (R20-014), Femicare.

New developments in the management of vulvovaginal atrophy: a comprehensive overview.

INTRODUCTION: Proper recognition and individualized therapy of vulvovaginal atrophy (VVA) is paramount. AREAS COVERED: Assessment of VVA should be performed using several questionnaires in combination with wet mount microscopy to determine Vaginal Cell Maturation Index (VCMI) and infections. PubMed searches were carried out between 1 march 2022 and 15 October 2022.Low dose vaginal estriol seems safe, efficient, and could be used in patients with contraindications for steroid hormones such as women with a history of breast cancer, and should therefore be considered as first choice hormonal treatment, when non-hormonal treatments fail. New estrogens, androgens, and several Selective Estrogen Receptor Modulators (SERMs) are being developed and tested. Intravaginal Hyaluronic Acid (HA) or Vit D can help women who can't or don't want to use hormones. EXPERT OPINION: Proper treatment is not possible without a correct and full diagnosis, including microscopy of the vaginal fluid. Low dose vaginal estrogen treatment, especially with estriol, is very efficient and is preferred in most women with VVA. Oral ospemifene and vaginal dihydroepiandrosterone (DHEA) are now considered efficient and safe alternative therapies for VVA. More safety data are waited for several SERMs and for a newly introduced estrogen: estetrol (E4), although so far no major side effects were seen from these drugs. Indications for laser treatments are questionable.

Lab-Based Retrospective 10-Year Analysis Shows Seasonal Variation of Vaginal Candida Infection Rates in Belgium.

Candida vulvovaginitis is a frequent condition, and although several risk factors are known, its behavior is still enigmatic. The seasonal influence of climate conditions and living habits on its prevalence was studied. In a retrospective lab-based cohort over 10 years, we studied the prevalence of Candida in 12,941 vaginal cultures taken from women attending a vulvovaginitis clinic. The prevalence of non-albicans and albicans species were compared per month to detect differences in positivity rates in summer versus winter months. Chi-square and chi-square for trend were used. Of the 2109 (16.3%) Candida spp. positive swabs, 201 (1.0%) revealed non-albicans species, varying between 1.0% and 2.0% per month, but without significant monthly differences. Over the 10 years, compared to other months, vaginal Candida was more frequent in June (19.0%, p = 0.008) and less frequent in December (14.5%, p = 0.04). The Candida prevalence was 15.5% in summer (June/July/August) versus 14.0% in the winter (Dec/Jan/Feb, p = 0.04). Change in temperature, dietary habits, and bodily adaptations due to increased amount of sunlight were discussed as potential pathophysiological mechanisms to explain the excess of Candida in summertime. Further confirmatory research would be beneficial. Women at risk for Candida vulvovaginitis should pay more attention to living habits in summertime to avoid recurrences.

Sperm quality and absence of SARS-CoV-2 RNA in semen after COVID-19 infection: a prospective, observational study and validation of the SpermCOVID test.

OBJECTIVE: To study the contagiousness of sperm and its influence on fertility after recovery from COVID-19 infection. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENT(S): One hundred twenty Belgian men who had recovered from proven COVID-19 infection. INTERVENTION(S): No intervention was performed. MAIN OUTCOME MEASURE(S): Semen quality was assessed using the World Health Organisation criteria. DNA damage to sperm cells was assessed by quantifying the DNA fragmentation index and the high density stainability. Finally antibodies against SARS-CoV2 spike-1 antigen, nuclear and S1-receptor binding domain were measured by Elisa and chemilumenscent microparticle immunoassays, respectively. RESULT(S): SARS-CoV-2 RNA was not detected in semen during the period shortly after infection nor at a later time. Mean progressive motility was reduced in 60% of men tested shortly (<1 month) after COVID-19 infection, 37% of men tested 1 to 2 months after COVID-19 infection, and 28% of men tested >2 months after COVID-19 infection. Mean sperm count was reduced in 37% of men tested shortly (<1 month) after COVID-19 infection, 29% of men tested 1 to 2 months after COVID-19 infection, and 6% of men tested >2 months after COVID-19 infection. The severity of COVID-19 infection and the presence of fever were not correlated with sperm characteristics, but there were strong correlations between sperm abnormalities and the titers of SARS-CoV-2 IgG antibody against spike 1 and the receptor- binding domain of spike 1, but not against nucleotide, in serum. High levels of antisperm antibodies developed in three men (2.5%). CONCLUSION(S): Semen is not infectious with SARS-CoV-2 at 1 week or more after COVID-19 infection (mean, 53 days). However, couples with a desire for pregnancy should be warned that sperm quality after COVID-19 infection can be suboptimal. The estimated recovery time is 3 months, but further follow-up studies are under way to confirm this and to determine if permanent damage occurred in a minority of men.

ISIDOG Consensus Guidelines on COVID-19 Vaccination for Women before, during and after Pregnancy.

INTRODUCTION: Sars-CoV-2 infection poses particular problems in pregnancy, as the infection more frequently causes severe complications than in unaffected pregnant women or nonpregnant women with SARS-CoV-2 infection. Now that vaccination is available and rapidly being implemented worldwide, the question arises whether pregnant women should be vaccinated, and if so, whether they should receive priority. METHODS: Available scientific data and available guidelines about vaccination against SARS-CoV-2 were collected by the Guideline Committee of the International Society of Infectious Diseases in Obstetrics and Gynecology (ISIDOG) and were analyzed, discussed and summarized as guidelines for healthcare workers caring for pregnant women. Concluding statements were graded according to the Oxford evidence-based medicine grading system. RESULTS: There is evidence to consider pregnancy as a risk factor for serious complications of COVID-19 infection, even in the absence of additional risk factors, such as hypertension, diabetes and obesity which increase these risks even more in pregnancy. Currently available data slightly favor mRNA-based vaccines above vector-based vaccines during pregnancy and breastfeeding, until more safety data become available. CONCLUSION: ISIDOG advises policy makers and societies to prioritize pregnant women to receive vaccination against SARS-CoV-2 and favor the mRNA vaccines until further safety information becomes available.

Genital Tract GAS Infection ISIDOG Guidelines.

There has been an increasing worldwide incidence of invasive group A streptococcal (GAS) disease in pregnancy and in the puerperal period over the past 30 years. Postpartum Group A streptococci infection, and in particular streptococcal toxic shock syndrome (TSS) and necrotizing fasciitis, can be life threatening and difficult to treat. Despite antibiotics and supportive therapy, and in some cases advanced extensive surgery, mortality associated with invasive group A streptococcal postpartum endometritis, necrotizing fasciitis, and toxic shock syndrome remains high, up to 40% of postpartum septic deaths. It now accounts for more than 75,000 deaths worldwide every year. Postpartum women have a 20-fold increased incidence of GAS disease compared to non-pregnant women. Despite the high incidence, many invasive GAS infections are not diagnosed in a timely manner, resulting in potentially preventable maternal and neonatal deaths. In this paper the specific characteristics of GAS infection in the field of Ob/Gyn are brought to our attention, resulting in guidelines to improve our awareness, early recognition and timely treatment of the disease. New European prevalence data of vaginal GAS colonization are presented, alongside two original case histories. Additionally, aerobic vaginitis is proposed as a supplementary risk factor for invasive GAS diseases.

ISIDOG Recommendations Concerning COVID-19 and Pregnancy.

Providing guidelines to health care workers during a period of rapidly evolving viral pandemic infections is not an easy task, but it is extremely necessary in order to coordinate appropriate action so that all patients will get the best possible care given the circumstances they are in. With these International Society of Infectious Disease in Obstetrics and Gynecology (ISIDOG) guidelines we aim to provide detailed information on how to diagnose and manage pregnant women living in a pandemic of COVID-19. Pregnant women need to be considered as a high-risk population for COVID-19 infection, and if suspected or proven to be infected with the virus, they require special care in order to improve their survival rate and the well-being of their babies. Both protection of healthcare workers in such specific care situations and maximal protection of mother and child are envisioned.

Screening for abnormal vaginal microflora by self-assessed vaginal pH does not enable detection of sexually transmitted infections in Ugandan women.

OBJECTIVE: Is self-assessed vaginal pH measurement to detect abnormal vaginal bacterial microflora (AVF) an adequate prescreening method for detection of genital sexually transmitted infections (STIs)? MATERIALS AND METHODS: A total of 360 Ugandan women tested themselves with a gloved finger and a pH color strip. PCR for bacterial vaginosis (BV)-associated bacteria was tested by PCR for Mycoplasma hominis, Ureaplasma urealyticum, and/or Atopobium vaginae, while the STIs were diagnosed by positive PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and/or Trichomonas vaginalis. RESULTS: A strong correlation was found between self-assessed pH values and BV-associated bacteria (P<0.0001), but not with STIs, not as single infections, nor in general. CONCLUSION: Self-measured vaginal pH correlated well with markers of high-risk microflora types such as BV or aerobic vaginitis, but not with STIs. Hence, in a screening program addressing AVF in low-resource countries, extra specific tests are required to exclude STIs.

Effect of short training on vaginal fluid microscopy (wet mount) learning.

OBJECTIVE: Is it feasible to learn the basics of wet mount microscopy of vaginal fluid in 10 hours? MATERIALS AND METHODS: This is a pilot project wherein 6 students with different grades of education were invited for being tested on their ability to read wet mount microscopic slides before and after 10 hours of hands-on training. Microscopy was performed according to a standard protocol (Femicare, Tienen, Belgium). Before and after training, all students had to evaluate a different set of 50 digital slides. Different diagnoses and microscopic patterns had to be scored. κ indices were calculated compared with the expert reading. RESULTS: All readers improved their mean scores significantly, especially for the most important types of altered flora (p < .0001). The mean increase in reading concordance (κ from 0.64 to 0.75) of 1 student with a solid previous experience with microscopy did not reach statistical significance, but the remaining 5 students all improved their scores from poor performance (all κ < 0.20) to moderate (κ = 0.53, n = 1) to good (κ > 0.61, n = 4) concordance. Reading quality improved and reached fair to good concordance on all microscopic items studied, except for the detection of parabasal cells and cytolytic flora. CONCLUSIONS: Although further improvement is still possible, a short training course of 10 hours enables vast improvement on wet mount microscopy accuracy and results in fair to good concordance of the most important variables of the vaginal flora compared to a reference reader.

Everolimus in acute kidney injury in a patient with breast cancer: a case report.

INTRODUCTION: Everolimus, a mammalian target of Rapamycin inhibitor, has recently been approved for the treatment of metastatic estrogen receptor-positive breast cancer, in combination with exemestane at a daily dose of 10mg. In the literature, few cases of acute kidney injury have been reported related to everolimus use, but none of them in a patient with breast cancer as we report here. Our case report of acute kidney injury demonstrates the potential nephrotoxic effects of everolimus therapy, necessitating close monitoring of renal function prior to, during and after discontinuation of the drug. CASE PRESENTATION: We report the first published case of acute kidney injury shortly after initiation of exemestane and everolimus for metastatic breast cancer resistant to letrozole in a 69-year-old Caucasian woman, initially treated for a stage IIB estrogen receptor-positive breast cancer in 1997. Within 2 weeks of therapy, she developed grade 1 to 2 diarrhea, lower extremity edema, lethargy, and anorexia. After 4 weeks of therapy, her blood pressure was 85/59 mmHg and she lost 4 kg bodyweight. Her serum creatinine was 3.34 mg/dL. Everolimus was stopped, and she was hospitalized for rehydration. Her serum creatinine levels peaked at 8.85 mg/dL 8 days after treatment discontinuation, with a calculated creatinine clearance of 7 mL/minute. Dialysis was not required. A month later, her serum creatinine levels slowly dropped to 2.26 mg/dL but did not return to baseline. No re-challenge of everolimus was attempted. CONCLUSIONS: Extreme vigilance should be used when prescribing everolimus for metastatic breast cancer. Although the exact cause of acute kidney injury in our case is unknown, dehydration must be avoided and renal function closely monitored after initiating therapy. Spontaneous recovery after drug discontinuation is possible.