SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Risk charts to identify low and excessive responders among first-cycle IVF/ICSI standard patients.

Ovarian stimulation carries a risk of either low or excessive ovarian response. The aim was to develop prognostic models for identification of standard (ovulatory and normal basal FSH) patients' risks of low and excessive response to conventional stimulation for IVF/intracytoplasmic sperm injection. Prospectively collected data on 276 first-cycle patients treated with 150 IU recombinant FSH (rFSH)/day in a long agonist protocol were analysed. Logistic regression analysis was applied to the outcome variables:low (seven or less follicles) and excessive (20 or more follicles) response. Variables were woman's age, menstrual cycle length, weight or body mass index, ovarian volume, antral follicle count (AFC) and basal FSH. The predictive performance of the models was evaluated from the prediction error (Brier score, %) where zero corresponds to a perfect prediction. Model stability was assessed using 1000 bootstrap cross-validation steps. The best prognostic model to predict low response included AFC and age (Brier score 7.94) and the best model to predict excessive response included AFC and cycle length (Brier score 15.82). Charts were developed to identify risks of low and excessive ovarian response. They can be used for evidence-based risk assessment before ovarian stimulation and may assist clinicians in individual dosage of their patients.

Individual versus standard dose of rFSH in a mild stimulation protocol for intrauterine insemination: a randomized study.

BACKGROUND: Controlled ovarian stimulation (COS) and intrauterine insemination (IUI) are often used as the first-line treatment for subfertile couples. To minimize the variability in ovarian response in patients' first treatment cycle, we recently developed a recombinant follicle-stimulating hormone (rFSH) dosage nomogram. The nomogram has now been tested. METHODS: Multicentre randomized controlled trial (RCT) including 228 ovulatory patients scheduled for COS and IUI. Patients were randomized to 'individual' (50-100 IU rFSH/day, n = 113) or 'standard' (75 IU rFSH/day, n = 115) dose. 'Individual' dose was prescribed according to the nomogram, which was based on patients' body weight and antral follicle count. The primary end-point was the proportion of patients with two to three follicles > or = 14 mm (maximum two follicles > or = 18 mm) on the day of hCG (leading follicle = 18 mm). Primary analysis was made by intention-to-treat. RESULTS: In the 'individual' group, 79/113 (70%) of the patients developed two to three follicles versus 64/115 (56%) in the 'standard' group [absolute difference = 14.3 percentage points; 95% confidence interval (CI) 2-26, P = 0.03; absolute difference = 14.4; 95% CI 2-27, P = 0.02, when adjusting for centre]. Among patients with two to three follicles, the proportion of patients with two follicles was 46/79 (58%) in the 'individual' group versus 34/64 (53%) in the 'standard' group, P = 0.54. Ongoing pregnancy rate was 23/113 (20%) in the 'individual' group and 21/115 (18%) in the 'standard' group and the rate of multiple gestations was 1/113 (1%) versus 5/115 (4%), P = 0.21. CONCLUSIONS: This RCT is the first to clinically test a dosage nomogram in ovulatory IUI patients' first rFSH treatment cycle. Dosing according to the nomogram was superior to standard dosing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00374634.