PP.36 The Impact of Unexplained Recurrent Miscarriage on Subsequent Pregnancy Outcomes

Systemic lupus erythematosus (SLE) often affects females of reproductive age and Cyclophosphamide, an alkylating agent leading to premature ovarian insufficiency (POF) and labelled category D for pregnancy is used as induction therapy for severe manifestations of lupus. There have been multiple case series reflecting variable outcomes of pregnancies after cyclophosphamide use for cancers and autoimmune diseases. With increasing maternal age, we have an increasing population of lupus patients who may wish to conceive after having received cyclophosphamide therapy. The objective of our study was to improve our understanding of the impact of cyclophosphamide exposure on fertility and pregnancy outcomes in patients with SLE. We retrospectively reviewed the charts of all patients who had received intravenous cyclophosphamide at our academic institute in the time period from 2000–2018 and identified 440 patients which included 157 female patients of reproductive age. There were 37 documented pregnancies after the cyclophosphamide infusion, of which 23 patients had successful outcomes; 4 elective abortion and 10 miscarriages. There were 17 patients who developed POF, of which 7 also had end stage renal disease. The average cumulative dose of cyclophosphamide in the patients who had successful pregnancy was 4080.37 mg compared to 2806.25 mg in those who had a miscarriage (p 0.164) and 5526.47 mg in those who developed POF (p 0.046). Using multiple regressions to evaluate risk factors impacting pregnancy outcomes, when taken as a set, the predictors including race, serological profile, exposure to steroids and Mycophenolate mofetil, age at cyclophosphamide infusion, age at pregnancy, and cumulative cyclophosphamide dose accounted for 46.29% of the variance in outcome of pregnancy (p 0.23) and 39.58% of the variance in development of premature ovarian failure (p 0.008). We noted statistical significance in the impact of maternal age at time of pregnancy (p 0.04) and duration of time between the last infusions to subsequent pregnancy (p 0.02) to pregnancy outcome. Our findings suggest that a longer time interval between the last cyclophosphamide infusion and subsequent pregnancy was favorable for a successful outcome and higher cumulative cyclophosphamide dose is more likely to be associated with premature ovarian failure.

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Pregnancy Outcomes of Women Conceiving on Antiretroviral Therapy (ART) Compared to Those Commenced on ART During Pregnancy

Clinical Infectious Diseases ◽

10.1093/cid/ciaa805 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gerhard Theron ◽

Sean Brummel ◽

Lee Fairlie ◽

Mauricio Pinilla ◽

Katie McCarthy ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Pregnancy Outcomes ◽

Subsequent Pregnancy ◽

Adverse Pregnancy Outcomes ◽

Childbearing Age ◽

Intention To Treat ◽

Increased Risk ◽

Breastfeeding Cessation ◽

Adverse Pregnancy ◽

The Impact

Abstract Background Globally, the number of infected women of childbearing age living with human immunodeficiency virus (HIV) and conceiving on antiretroviral therapy (ART) is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The Promoting Maternal and Infant Survival Everywhere (PROMISE) 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. Methods The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of nonbreastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who restarted ART after pregnancy was diagnosed. Results Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (<2500 g) for women who conceived while on ART (relative risk, 2.65 [95% confidence interval {CI}, 1.20–5.81]), and also a higher risk of spontaneous abortion, stillbirth, or neonatal death (hazard ratio, 1.40 [95% CI, .99–1.98]) compared to women who restarted ART after they were found to be pregnant during trial follow-up. Conclusions We found an increased risk for adverse pregnancy outcomes in women conceiving on ART, emphasizing the need for improved obstetric and neonatal care for this group. Clinical Trials Registration NCT01061151.

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The role of the renin–angiotensin system in regulating endometrial neovascularization during the peri-implantation period: literature review and preliminary data

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820920560 ◽

2020 ◽

Vol 11 ◽

pp. 204201882092056 ◽

Cited By ~ 1

Author(s):

Ruofan Qi ◽

Tin Chiu Li ◽

Xiaoyan Chen

Keyword(s):

Angiotensin Ii ◽

Pilot Study ◽

Literature Review ◽

Pregnancy Outcomes ◽

Recurrent Miscarriage ◽

Renin Angiotensin System ◽

Subsequent Pregnancy ◽

Angiotensin System ◽

Implantation Period

Background: Implantation is initiated when the blastocyst attaches to the endometrium during the peri-implantation period, and appropriate neovascularization is a prerequisite for the success of the subsequent process. The role of the renin–angiotensin system (RAS) in regulation of blood pressure and hydro-electrolyte balance has long been recognized, while its role in the peri-implantation endometrium remains unclear. This manuscript discusses endometrial RAS and its possible pathways in regulating endometrial angiogenesis and its influence on subsequent pregnancy outcomes. Methods: A comprehensive search of electronic databases was carried out to identify relevant published articles, and a literature review was then performed. Using immunohistochemistry, we also performed a pilot study to examine expression of angiotensin II receptors, including angiotensin II type 1 (AT1) receptor (AT1-R) and angiotensin II type 2 (AT2) receptor (AT2-R) in the human endometrium around the time of implantation. Results: The results of the pilot study showed expression of AT1-R and AT2-R in all endometrial compartments (luminal epithelium, glandular epithelium, stroma cells, and blood vessels), and altered expression was witnessed in women with recurrent miscarriage when compared with fertile control women from our preliminary result. Conclusion: Altered vasculature of the endometrium in the peri-implantation period is detrimental to implantation and may lead to recurrent miscarriage. Being an angiogenic mediators, endometrial RAS may play a role around the time of embryo implantation, affecting subsequent pregnancy outcomes.

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