Prospective reproductive outcomes according to sperm parameters, including DNA fragmentation, in recurrent pregnancy loss.

RESEARCH QUESTION: Are the prospective reproductive outcomes in couples experiencing recurrent pregnancy loss (RPL) related to the sperm DNA fragmentation index (DFI), as measured by sperm chromatin structure assay, sperm morphology and sperm concentration at referral? DESIGN: This prospective cohort study included 95 couples seen between 1 April 2018 and 1 December 2019 at the tertiary Copenhagen RPL Unit, Copenhagen University Hospital, Rigshospitalet and Hvidovre Hospital, Denmark. The couples had experienced three or more unexplained consecutive pregnancy losses or two late pregnancy losses (>12 weeks gestation). Follow-up was 12-31 months. RESULTS: Eighty-one of 95 (85.3%) couples achieved pregnancy after referral. In the first pregnancy after referral, 46 (56.8%) couples achieved a live birth, and 35 (43.2%) couples experienced another pregnancy loss. There was no significant difference in baseline DFI between couples that experienced pregnancy loss [median 11.7, interquartile range (IQR) 9.1-17.3] and couples that achieved a live birth (median 12.5, IQR 9.3-16.5; P = 0.971). Improving sperm morphology increased the odds of a live birth after referral (adjusted OR 1.26, 95% CI 1.05-1.52; P = 0.014). DFI and sperm concentration were not associated with the outcome of the first pregnancy after referral. Overall, 35.9% of the men had DFI ≥15 at inclusion. Couples that failed to achieve pregnancy had a higher median DFI of 17.7 (IQR 7.7-27.2) compared with the rest of the cohort (median 12.0, IQR 9.3-16.5; P = 0.041). CONCLUSIONS: At referral, sperm DFI, morphology and concentration cannot be used to identify RPL couples at risk of another pregnancy loss. Increased baseline DFI was associated with difficulty achieving another pregnancy, and improving sperm morphology was associated with increased odds of a live birth.

Smoking and recurrent pregnancy loss: A cohort study of 2829 women.

Smoking during pregnancy is associated with negative reproductive outcome. Less is known about the impact of smoking or previous smoking in women with recurrent pregnancy loss (RPL) which this study aimed to investigate. We included all women <42 years (n=2829) referred to a RPL unit at Copenhagen University Hospital between January 2000 and December 2021 in the cohort with follow-up until June 2022. Patients were categorized as 'smokers at time of referral', 'never-smokers' or 'former smokers'. The main outcomes were pregnancy history prior to referral, prospective pregnancy rate, live birth rate, rates of ectopic pregnancy, and stillbirth. At referral, smokers (n=373) were on average 2.0 years younger (P<0.001) and had experienced significantly more pregnancy losses (P<0.001), and stillbirths (P=0.01) compared to never-smokers (n=2100). Former smokers had a higher risk of stillbirth prior to referral compared to never-smokers but no differences in pregnancy rate or other outcomes. Prospective pregnancy rates were lower for smokers compared with never-smokers (71.8% vs. 77.5%, P=0.02). Live birth rate was 58.0% for the 243 women who smoked at referral compared to 61.4% for the 1488 never-smokers (P=0.32). Stillbirth and ectopic pregnancies were significantly more common for smokers (2.8% vs. 0.4%, P=0.01; 6.0% vs. 2.0%, P<0.008). Women with RPL who smoked at referral were referred younger with a higher number of previous pregnancy losses and stillbirths compared with never-smokers. Fewer smokers achieved a pregnancy after referral but those who did had a similar live birth rate compared to never-smokers, although stillbirths and ectopic pregnancies were more common.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies at Delivery in Women, Partners, and Newborns.

OBJECTIVE: To investigate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in parturient women, their partners, and their newborns and the association of such antibodies with obstetric and neonatal outcomes. METHODS: From April 4 to July 3, 2020, in a single university hospital in Denmark, all parturient women and their partners were invited to participate in the study, along with their newborns. Participating women and partners had a pharyngeal swab and a blood sample taken at admission; immediately after delivery, a blood sample was drawn from the umbilical cord. The swabs were analyzed for SARS-CoV-2 RNA by polymerase chain reaction, and the blood samples were analyzed for SARS-CoV-2 antibodies. Full medical history and obstetric and neonatal information were available. RESULTS: A total of 1,313 parturient women (72.5.% of all women admitted for delivery at the hospital in the study period), 1,188 partners, and 1,206 newborns participated in the study. The adjusted serologic prevalence was 2.6% in women and 3.5% in partners. Seventeen newborns had SARS-CoV-2 immunoglobulin G (IgG) antibodies, and none had immunoglobulin M antibodies. No associations between SARS-CoV-2 antibodies and obstetric or neonatal complications were found (eg, preterm birth, preeclampsia, cesarean delivery, Apgar score, low birth weight, umbilical arterial pH, need for continuous positive airway pressure, or neonatal admission), but statistical power to detect such differences was low. Full serologic data from 1,051 families showed an absolute risk of maternal infection of 39% if the partner had antibodies. CONCLUSION: We found no association between SARS-CoV-2 infection and obstetric or neonatal complications. Sixty-seven percent of newborns delivered by mothers with antibodies had SARS-CoV-2 IgG antibodies. A limitation of our study is that we lacked statistical power to detect small but potentially meaningful differences between those with and without evidence of infection.

Determinants of monozygotic twinning in ART: a systematic review and a meta-analysis.

BACKGROUND: The incidence of monozygotic twins (MZT) after ART appears to be higher than the incidence after spontaneous conceptions contradicting the aim of ART to avoid multiple pregnancies because of the associated risks. OBJECTIVE AND RATIONALE: The aim was to study the frequency of MZT after IVF and ICSI and how it is influenced by the day of embryo transfer, maternal age, zona pellucida manipulation, controlled ovarian stimulation, stimulation protocol, culture media and embryo quality. SEARCH METHODS: Original studies and reviews were identified by searching the PubMed, Embase and Cochrane databases up to March 2017. The inclusion criterion was publications focusing on the five study questions related to MZT in our study. The exclusion criteria were articles that did not include blastocyst transfer, were on non-humans, were not published in peer-reviewed journals, and were based only on case studies. All of the articles were categorized according to the Oxford Centre for Evidence-based Medicine's 'Levels of Evidence', and quality and risk of bias assessment was performed with 'The Cochrane Collaboration's Risk of Bias Tools'. A meta-analysis was performed to study the impact of the day of embryo transfer on the MZT rate. OUTCOMES: The literature search resulted in a total of 42 articles, including 38 original studies, for analysis. The included original studies reported a MZT rate with blastocyst transfer from zero to 13.2%. Our meta-analysis found a higher frequency of MZT after blastocyst transfer compared with cleavage-stage embryos transfer: odds ratio = 2.18, 95% CI: 1.93-2.48 (fixed effect meta-analysis). A younger maternal age may increase the MZT rate, and recent studies regarding the use of zona pellucida manipulating techniques have disagreed with the previous suspicion of a higher MZT rate after the use of these methods. The extended culture to-blastocyst stage is a potential risk factor for MZT, but it is uncertain whether this phenomenon is due to the extended time, culture media or greater likelihood of younger oocytes to reach the blastocyst stage. An increased frequency of MZT following the GnRH-agonist suppression protocol has been suggested, as well as a decreased frequency of MZT with high gonadotrophin doses, which could reflect an age-related effect. Only limited literature has focused on the role of embryo morphology in the MZT rate, therefore, this issue remains unresolved. WIDER IMPLICATIONS: We found blastocyst transfer to be a risk factor for MZT. Hence, the results of this meta-analysis may weaken the previously proposed view that greater experience with blastocyst transfer and improved culture media could decrease the high rate of MZT after blastocyst transfer. To minimize the rate of MZT and the associated complications, the mechanisms underlying blastocyst transfer and MZT pregnancy must be elucidated.