COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.

The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood. This review evaluates the published literature on COVID-19 and its impact on menstrual bleeding, discussing the strengths and limitations of these studies. We present evidence consistent with SARS-CoV-2 infection and long COVID having an association with changes in menstrual bleeding parameters and that the impact of COVID vaccination on menstruation appears less significant. An overview of menstrual physiology and known causes of abnormal uterine bleeding (AUB) is provided before discussing potential mechanisms which may underpin the menstrual disturbance reported with COVID-19, highlighting areas for future scientific study. Finally, consideration is given to the effect that menstruation may have on COVID-19, including the impact of the ovarian sex hormones on acute COVID-19 severity and susceptibility and reported variation in long COVID symptoms across the menstrual cycle. Understanding the current evidence and addressing gaps in our knowledge in this area are essential to inform public health policy, direct the treatment of menstrual disturbance and facilitate development of new therapies, which may reduce the severity of COVID-19 and improve quality of life for those experiencing long COVID.

Short versus extended progesterone supplementation for luteal phase support in fresh IVF cycles: a systematic review and meta-analysis.

This review and meta-analysis aim to assess the effect of prolonged progesterone support on pregnancy outcomes in women undergoing fresh embryo transfer after IVF/intracytoplasmic sperm injection (ICSI). Two independent authors searched Embase, MEDLINE and grey literature from inception to January 2019 for randomized controlled trials (RCT) of prolonged progesterone support versus early cessation. Risk of bias was assessed. Outcome measures were live birth, miscarriage and ongoing pregnancy rate. The study was registered with PROSPERO (CRD42018088605). Seven trials involving 1627 participants were included: three reported live birth rate (672/830), seven the miscarriage rate (178/1627) and seven the ongoing pregnancy rate (1351/1627). Clinical outcomes were similar between early progesterone cessation versus progesterone continuation: live birth rate (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.88-1.00), miscarriage rate (RR 0.91, 95% CI 0.69-1.20) and ongoing pregnancy rate (RR 0.98, 95% CI 0.91-1.05). Ongoing pregnancy rates were similar when analyses were restricted to those with cessation of progesterone on the day of a positive human chorionic gonadotrophin (RR 0.93, 95% CI 0.83-1.06). This meta-analysis suggests that prolonged progesterone support may be unnecessary after fresh embryo transfer. Further larger RCT would be useful to corroborate and lead to standardized duration of progesterone luteal phase support across IVF/ICSI centres.

Uterine miR-877-3p and let-7a-5p are increased during simulated menstruation in a mouse model.

Heavy periods are common and debilitating, but we do not fully understand how they are caused. Increased understanding of menstrual bleeding could result in new treatments for problematic periods. Low oxygen levels are present in the womb lining during a period. These low oxygen levels help trigger the repair process required to stop menstrual bleeding. MicroRNAs (miRNAs) are small molecules that can affect cell function, and some are regulated by oxygen levels. We examined whether such miRNAs were present in the womb lining during a period. To overcome the variability present in humans, we studied the womb of mice given hormones to mimic the human menstrual cycle. We revealed that two miRNAs known to be regulated by oxygen levels were increased in the womb during menstruation. These miRNAs may help regulate menstrual blood loss and merit further study as a potential target for future treatments for heavy periods.

The Menstrual Endometrium: From Physiology to Future Treatments.

Abnormal uterine bleeding (AUB) is experienced by up to a third of women of reproductive age. It can cause anaemia and often results in decreased quality of life. A range of medical and surgical treatments are available but are associated with side effects and variable effectiveness. To improve the lives of those suffering from menstrual disorders, delineation of endometrial physiology is required. This allows an increased understanding of how this physiology may be disturbed, leading to uterine pathologies. In this way, more specific preventative and therapeutic strategies may be developed to personalise management of this common symptom. In this review, the impact of AUB globally is outlined, alongside the urgent clinical need for improved medical treatments. Current knowledge of endometrial physiology at menstruation is discussed, focusing on endocrine regulation of menstruation and local endometrial inflammation, tissue breakdown, hypoxia and endometrial repair. The contribution of the specialised endometrial vasculature and coagulation system during menstruation is highlighted. What is known regarding aberrations in endometrial physiology that result in AUB is discussed, with a focus on endometrial disorders (AUB-E) and adenomyosis (AUB-A). Gaps in existing knowledge and areas for future research are signposted throughout, with a focus on potential translational benefits for those experiencing abnormal uterine bleeding. Personalisation of treatment strategies for menstrual disorders is then examined, considering genetic, environmental and demographic characteristics of individuals to optimise their clinical management. Finally, an ideal model of future management of AUB is proposed. This would involve targeted diagnosis of specific endometrial aberrations in individuals, in the context of holistic medicine and with due consideration of personal circumstances and preferences.

Phenytoin-induced hypothermia.

A 60-year-old man with cerebral palsy and epilepsy was admitted with acute lethargy and deterioration in coordination. He was noted to be hypothermic at 35°C on admission. Routine work-up revealed toxic levels of phenytoin. No cause of hypothermia could be identified but as his phenytoin levels normalised, his body temperature also improved. There are three other reported cases of phenytoin- induced hypothermia in the literature. Could this be a rare cause of hypothermia?