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Research question The definition of recurrent pregnancy loss (RPL) differs internationally. The European Society of Human Reproduction and Embryology (ESHRE) defines RPL as two or more pregnancy losses. Different definitions lead, however, to different approaches to care for couples with RPL. This study aimed to determine whether the distribution of RPL-associated factors was different in couples with two versus three or more pregnancy losses. If a similar distribution were found, couples with two pregnancy losses should be eligible for the same care pathway as couples with three pregnancy losses. Design This single-centre, retrospective cohort study investigated 383 couples included from 2012 to 2016 at the Leiden University Medical Center RPL clinic. Details on age, body mass index, smoking status, number of pregnancy losses, mean time to pregnancy loss and performed investigations were collected. The prevalence of uterine anomalies, antiphospholipid syndrome, hereditary thrombophilia, hyperhomocysteinaemia, chromosomal abnormalities and positive thyroid peroxidase antibodies were compared in couples with two versus three or more pregnancy losses. Results No associated factor was found in 71.5% of couples with RPL. This did not differ statistically between couples with two versus three or more pregnancy losses (73.6% versus 70.6%; P = 0.569). The distribution of investigated causes did not differ between the two groups. Conclusions As the distribution of associated factors in couples with two versus three or more pregnancy losses is equal, couples with two pregnancy losses should be eligible for the same care pathway as couples with three. This study supports ESHRE's suggestion of including two pregnancy losses in the definition of RPL.

INTRODUCTION: The cause of recurrent pregnancy loss often remains unknown. Possibly, pathophysiological pathways are shared with other pregnancy complications. MATERIAL AND METHODS: All women with secondary recurrent pregnancy loss (SRPL) visiting Leiden University Medical Center (January 2000-2015) were included in this retrospective cohort to assess whether women with SRPL have a more complicated first pregnancy compared with control women. SRPL was defined as three or more consecutive pregnancy losses before 22 weeks of gestation, with a previous birth. The control group consisted of all Dutch nullipara delivering a singleton (January 2000-2015). Information was obtained from the Dutch Perinatal Registry. Outcomes were preeclampsia, preterm birth, post-term birth, intrauterine growth restriction, breach position, induction of labor, cesarean section, congenital abnormalities, perinatal death and severe hemorrhage in the first ongoing pregnancy. Subgroup analyses were performed for women with idiopathic SRPL and for women ≤35 years. RESULTS: In all, 172 women with SRPL and 1 196 178 control women were included. Women with SRPL were older and had a higher body mass index; 29.7 years vs. 28.8 years and 25.1 kg/m2 vs. 24.1 kg/m2 , respectively. Women with SRPL more often had a post-term birth (OR 1.86, 95% CI 1.10-3.17) and more perinatal deaths occurred in women with SRPL compared with the control group (OR 5.03, 95% CI 2.48-10.2). Similar results were found in both subgroup analyses. CONCLUSIONS: The first ongoing pregnancy of women with (idiopathic) SRPL is more often complicated by post-term birth and perinatal death. Revealing possible links between SRPL and these pregnancy complications might lead to a better understanding of underlying pathophysiology.

Objective Follow-up of IVF/intracytoplasmic sperm injection (ICSI) patients to obtain accurate information concerning chances of live birth as well as early treatment dropout. Comparison of the cumulative pregnancy rates, established in cohorts, with those estimated with life table analysis to determine which method provides the most accurate data without overestimation. Design Retrospective longitudinal cohort study. Setting Academic medical IVF center. Patient(s) All 750 patients from the Leiden IVF center and another 706 patients from cooperating clinics starting IVF/ICSI treatment in the period 1996–2000. Intervention(s) All observations were part of standard IVF/ICSI and cryopreservation protocols. Main Outcome Measure(s) Endpoints of this study were a first live birth or termination of treatment. Treatment cycles were followed until the end of 2002, pregnancy follow-up through September 2003. Result(s) The cumulative live birth rate for the Leiden cohort was 59.1%. In yearly cohorts this varied from 54.8% to 67.1%. Cumulative live birth rates were 61.8%–63.2% for unexplained infertility (n = 229), endometriosis (n = 19), and andrologic indication (n = 223). For tubal (n = 129) and hormonal (n = 46) indications the rates were 55.8% and 45.7%, respectively. The group of egg donation or surrogacy (n = 10) reached 40.0%, and patients with two or more indications (n = 84) 56.0%. For women ≤35 years of age the cumulative live birth rate was 64.6%, for women 36–39 years of age it was 48.7%, and for women 40–42 years of age 31.0%. Conclusion(s) In contrast to estimation of expected cumulative pregnancy rates the cohort measurement does not overestimate success rates. It accurately reflects chances of both live birth as well as early treatment dropout. The cumulative live birth rate was 59.1%. Over time results improved and the contribution of cryopreservation increased.

Objective To determine whether patients with borderline semen should be treated with conventional IVF or intracytoplasmic sperm injection (ICSI). Design Randomized study. Setting A university medical center in The Netherlands. Patient(s) One hundred six couples with borderline semen who were undergoing IVF and ICSI on sibling oocytes. Intervention(s) Performing IVF and ICSI on sibling oocytes. Main Outcome Measure(s) Fertilization and pregnancy rates. Result(s) One thousand five hundred eighteen oocytes were collected in 106 oocyte retrievals: 849 oocytes were randomly allocated to ICSI, of which 761 were microinjected, and 669 oocytes were randomly assigned to IVF. In 26 of the 106 patients, there was fertilization only after ICSI and not after IVF (IVF− group). The fertilization rate was 51% (92/182 oocytes). In 78 patients, there was fertilization after both IVF and ICSI (IVF+ group); the fertilization rate was 51% for both the IVF- and ICSI-treated oocytes (271/528 oocytes and 334/658 oocytes, respectively). In 2 patients, there was no fertilization after either IVF (0/6 oocytes) or ICSI (0/9 oocytes). Patients of the IVF+ group had a higher total motile sperm count after preparation than did those of the IVF− group. More high-quality embryos were obtained after ICSI in patients of the IVF+ group. In 101 patients, embryo transfer was performed: 26 in the IVF− group and 75 in the IVF+ group. No significant differences were found with regard to pregnancy rates between those two groups: pregnancy rates were 54% in the IVF− group and 48% in the IVF+ group. Conclusion(s) Performing ICSI on at least some of the oocytes will avoid unnecessary fertilization failure in patients with borderline semen: in this study, 26 of 104 cycles (25%) were rescued by ICSI.