Live Birth Pregnancy Research Articles

Maternal interpregnancy weight change and premature birth: Findings from an English population-based cohort study.

BackgroundThe relationship between maternal weight change between pregnancies and premature birth is unclear. This study aimed to investigate whether interpregnancy weight change between first and second, or second and third pregnancy is associated with premature birth.MethodsRoutinely collected data from 2003 to 2018 from one English maternity centre was used to produce two cohorts. The primary cohort (n = 14,961 women) consisted of first and second live-birth pregnancies. The secondary cohort (n = 5,108 women) consisted of second and third live-birth pregnancies. Logistic regression models were used to examine associations between interpregnancy BMI change and premature births adjusted for confounders. Subgroup analyses were carried out, stratifying by initial pregnancy BMI groups and analysing spontaneous and indicated premature births separately.ResultsIn the primary cohort, 3.4% (n = 514) of births were premature compared to 4.2% (n = 212) in the secondary cohort, with fewer indicated than spontaneous premature births in both cohorts.Primary cohortWeight loss (>3kg/m2) was associated with increased odds of premature birth (adjusted odds ratio (aOR):3.50, 95% CI: 1.78–6.88), and spontaneous premature birth (aOR: 3.34, 95%CI: 1.60–6.98), in women who were normal weight (BMI 18.5-25kg/m2) at first pregnancy. Weight gain >1kg/m2 was not associated with premature birth regardless of starting BMI.Secondary cohortLosing >3kg/m2 was associated with increased odds of premature birth (aOR: 2.01, 95%CI: 1.05–3.87), when analysing the whole sample, but not when restricting the analysis to women who were overweight or obese at second pregnancy.ConclusionsNormal-weight women who lose significant weight (>3kg/m2) between their first and second live pregnancies have greater odds of premature birth compared to normal-weight women who remain weight stable in the interpregnancy period. There was no evidence of association between weight change in women who were overweight or obese at the start of their first pregnancy and premature birth.

Hydroxyurea Exposure throughout Pregnancy in Patients with Sickle-Cell Disease : 4 Case Reports from European Non-Interventional, Multicentric, Prospective Escort-HU Study

Over the last decades, the number of sickle-cell disease (SCD) women reaching childbearing age and planning to become pregnant is increasing due to improvements in the management of the disease.[1] Physiological changes of pregnancy, such as increased metabolic demand, increased blood viscosity and hyper-coagulability, lead to an increased incidence of complications, such as vaso-occlusive crisis (VOC), acute chest syndrome (ACS), osteonecrosis, hepatic necrosis, leg ulcers, and thromboembolic events. [2] Vaso-occlusion may also involve the placenta, with villi fibrosis, necrosis, and infarction leading to impaired uteroplacental circulation, with consequent chronic fetal hypoxia and adverse fetal outcomes. Therefore, prenatal care is important to evaluate if intensification of treatment as blood transfusion or Hydroxyurea (HU) may be required. HU is approved in EU and USA for VOC including ACS in patients with SCD aged 2 years and over. HU is not recommended for use during pregnancy, primarily because animal studies have suggested potential teratogenic effects on the fetus. In some rare cases, discontinuation of HU treatment to avoid fetal exposure is not possible. A few cases of exposure to HU throughout the pregnancy are published in the literature,[3] but none in SCD patients. We hereby present four cases in which HU was taken during all pregnancy collected in the ESCORT-HU study (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study which collected long-term safety information on HU when used in current practice. Patient #1 (GxP2, SS) had a history of VOC, osteonecrosis and leg ulcers and was started on HU at age 18. She had two previous pregnancies without HU exposure. No oral contraception was taken and she spontaneously conceived at age 37. HU was continued at the same dose. Patient #2 (G5P1, Sβ+) had a history of VOC, chronic anemia and heart disease, and was started on HU at age 19. At age 34, she started to receive treatment for fertility (gonadotropin and follitropin). HU which had been started 17 years earlier was continued. Patient #3 (G5P1, Sβ+) had a history of chronic severe anemia and was started on HU at age 37. She had a gynecological history of 1 spontaneous abortion, 2 elective abortions and 1 live birth (pregnancy complicated with preeclampsia). She had been on oral contraception before becoming spontaneously pregnant when aged 38. HU, which had been initiated 11 months earlier, was continued at same dose. Patient #4 (SS, G3P0) female with history of stroke with sequelae and VOC, initiated on HU at the age of 25 following post-transfusion alloimmunization. Gynecological history included one spontaneous abortion and one elective abortion when aged 21 and 23 years (before initiation of HU). Following removal of contraceptive device, she conceived spontaneously at age 27. These four women suffered from severe SCD symptoms which required special management during pregnancies. HU exposure during pregnancy is not recommended but these case reports highlight the difficulty for medical teams to deal with both strong desire to become pregnant and maternal and fetal morbidity and mortality in SCD. Similarly to literature data in non-SCD patients, all four pregnancies in SCD women with HU exposure throughout pregnancy had a favorable outcome and no malformation was reported among the neonates. Details of pregnancy course and outcome are provided in Table 1. Although it is highly recommended to avoid any fetal exposure to HU, it can be difficult in some SCD patients with severe symptoms and a wish to become pregnant, to stop the treatment during pregnancy. In these cases, a strict monitoring of the mother and fetus is necessary. [1] Silva F.A.C., Ferreira A.L.C.G., Hazin-Costa M.F., Dias M.L.G., Araújo A.S., Souza A.I., Adverse clinical and obstetric outcomes among pregnant women with different sickle cell disease genotypes, International Federation of Gynecology and Obstetrics, 2018 [2] Jain D., Atmapoojya P., Colah R., Lodha P. Sickle cell disease and pregnancy. Mediterr J Hematol Infect Dis 2019, 11(1): e2019040 [3] C Thauvin-Robinet, Exposure to hydroxyurea during pregnancy: a case series, Correspondence 2001 Disclosures No relevant conflicts of interest to declare.

Maternal reproductive history and premenopausal risk of hypertension and cardiovascular disease: a Danish cohort study

ObjectivesThe metabolic changes of pregnancy resemble a cardiovascular risk profile and may persist postpartum, with body mass index (BMI) as a potential modifier. We examined the association between the number...

Reproductive Outcomes Following Uterine Artery Occlusion at the Time of Myomectomy: Systematic Review and Meta-analysis.

This investigation sought systematically to review and meta-analyze evidence on reproductive outcomes following uterine artery occlusion (UAO) at myomectomy. Databases searched included PubMed, EMBASE, Ovid MEDLINE, Web of Science, and ClinicalTrials.gov. Eligible studies included observational and randomized controlled trials in which patients underwent abdominal, laparoscopic, or robotic myomectomy and in which at least one measure of clinical pregnancy rate, live birth rate, or ovarian reserve was reported. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy rate, miscarriage rate, adverse pregnancy outcomes, and measures of ovarian reserve. Twelve articles involving 689 women were included in the systematic review. The intervention group underwent UAO at laparoscopic or abdominal myomectomy (UAO+M) (n = 470). The control group underwent myomectomy alone (n = 219). Seven articles involving 420 women were included in the meta-analysis (201 underwent UAO+M; 219 underwent myomectomy alone). Live births occurred in 54 of 201 (27%) women in the UAO+M group and in 74 of 219 (34%) women in the control group. Clinical pregnancies occurred in 73 of 201 (36%) women in the UAO+M group and in 102 of 219 (47%) control subjects. There was no difference in live birth rates (odds ratio 0.89; 95% CI 0.56-1.43; P = 0.51; 7 studies, 420 patients) or clinical pregnancy rates (odds ratio 0.81; 95% confidence interval 0.53-1.24; P = 0.33; 7 studies, 420 patients) between the UAO+M and control groups. Data on miscarriage rates, adverse pregnancy outcomes, and measures of ovarian reserve precluded meta-analysis. In conclusion, UAO at myomectomy is not associated with reductions in live birth or clinical pregnancy rates. Before routine use can be recommended in women desiring future fertility, more research is required on reproductive outcomes and effects on ovarian reserve.

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.

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

National population-based estimates for major birth defects, 2010-2014.

Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014. Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time. The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18. National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.

Effects of physical exercises on semen quality and reproductive outcomes in male infertility: A protocol for systematic review and meta-analysis of randomized controlled trials.

Background:Infertility has troubled the world's 186 million people, and male infertility accounts for more than half. The literature of physical exercise related to semen quality has shown inconsistent results, and there is currently no systematic review to evaluate the effects of exercise on reproductive outcomes in male infertility patients. This study aims to assessing the effects of exercise interventions based on randomized controlled trials (RCTs) on semen quality and reproductive outcomes in male infertility.Methods:English and Chinese literature about physical exercise treatment for male infertility published before July 31, 2019 will be systematic searched in PubMed, Embase, Web of Science, Cochrane Library, Open Grey, Clinicaltrials.gov, Chinese Clinical Trial Registry, WANFANG, VIP Chinese Science and Technology Journal Database, CNKI, Chinese biomedical document service system (SinoMed). Only RCTs of patients with male infertility will be included. Literature screening, data extraction, and the assessment of risk of bias will be independently conducted by 2 reviewers, and the 3rd reviewer will be consulted if any different opinions existed. Live-birth rate, pregnancy rate, adverse events (including miscarriage), sperm concentration, progressive motility, sperm morphology, and sperm DNA fragmentation will be evaluated. Systematic review and meta-analysis will be produced by RevMan 5.3 and Stata 14.0. This protocol reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement.Conclusion and dissemination:We will assess the efficacy and safety of physical exercise on semen quality and reproductive outcomes in infertile men. The findings will be published in a peer-reviewed journal to provide evidence-based medical evidence for clinical decision making and the patient's lifestyle guidance.Registration information:PROSPERO CRD42019140294

Endometrial thickness and IVF cycle outcomes: a meta-analysis.

In this meta-analysis, the association between endometrial thickness (EMT) and cycle outcomes after IVF is explored. Associations between EMT and cycle outcomes according to study and individual characteristics were also assessed. Studies evaluating associations between EMT and pregnancy, implantation, miscarriage, live birth or ongoing pregnancy and ectopic pregnancy rates in individuals after IVF were identified on PubMed, Embase and the Cochrane Library (from their inception up to December 2018). Pooled odds ratios with 95% confidence intervals, calculated using the random-effects model, were used. Nine prospective and 21 retrospective studies, including a total of 88,056 cycles, were retrieved. The summary odds ratios indicated that women with lower EMT were associated with lower pregnancy rates than those with higher EMT (n = 30, OR 0.61; 95% CI 0.52 to 0.70; P < 0.001). Moreover, the implantation rate in women with lower EMT was significantly reduced (n = 9, OR 0.49; 95% CI 0.32 to 0.74; P = 0.001). Furthermore, no significant association was found between EMT and the miscarriage rate (n = 12). In addition, women with lower EMT were associated with reduced live birth or ongoing pregnancy rate (11 studies, OR 0.60; 95% CI 0.48 to 0.73; P < 0.001). Finally, the incidence of ectopic pregnancy rate between lower and higher EMT showed no statistically significant association (n = 3). Lower EMT was associated with lower pregnancy, implantation and live birth or ongoing pregnancy rates.

Interventions for unexplained infertility: a systematic review and network meta-analysis.

Clinical management for unexplained infertility includes expectant management as well as active treatments, including ovarian stimulation (OS), intrauterine insemination (IUI), OS-IUI, and in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI).Existing systematic reviews have conducted head-to-head comparisons of these interventions using pairwise meta-analyses. As this approach allows only the comparison of two interventions at a time and is contingent on the availability of appropriate primary evaluative studies, it is difficult to identify the best intervention in terms of effectiveness and safety. Network meta-analysis compares multiple treatments simultaneously by using both direct and indirect evidence and provides a hierarchy of these treatments, which can potentially better inform clinical decision-making. To evaluate the effectiveness and safety of different approaches to clinical management (expectant management, OS, IUI, OS-IUI, and IVF/ICSI) in couples with unexplained infertility. We performed a systematic review and network meta-analysis of relevant randomised controlled trials (RCTs). We searched electronic databases including the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane Central Register of Studies Online, MEDLINE, Embase, PsycINFO and CINAHL, up to 6 September 2018, as well as reference lists, to identify eligible studies. We also searched trial registers for ongoing trials. We included RCTs comparing at least two of the following clinical management options in couples with unexplained infertility: expectant management, OS, IUI, OS-IUI, and IVF (orcombined with ICSI). Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardised forms. The primary effectiveness outcome was a composite of cumulative live birth or ongoing pregnancy, and the primary safety outcome was multiple pregnancy. We performed a network meta-analysis within a random-effects multi-variate meta-analysis model. We presented treatment effects by using odds ratios (ORs) and 95% confidence intervals (CIs). For the network meta-analysis, we used Confidence in Network Meta-analysis (CINeMA) to evaluate the overall certainty of evidence. We included 27 RCTs (4349 couples) in this systematic review and 24 RCTs (3983 couples) in a subsequent network meta-analysis. Overall, the certainty of evidence was low to moderate: the main limitations were imprecision and/or heterogeneity.Ten RCTs including 2725 couples reported on live birth. Evidence of differences between OS, IUI, OS-IUI, or IVF/ICSI versus expectant management was insufficient (OR 1.01, 95% CI 0.51 to 1.98; low-certainty evidence; OR 1.21, 95% CI 0.61 to 2.43; low-certainty evidence; OR 1.61, 95% CI 0.88 to 2.94; low-certainty evidence; OR 1.88, 95 CI 0.81 to 4.38; low-certainty evidence). This suggests that if the chance of live birth following expectant management is assumed to be 17%, the chance following OS, IUI, OS-IUI, and IVF would be 9% to 28%, 11% to 33%, 15% to 37%, and 14% to 47%, respectively. When only including couples with poor prognosis of natural conception (3 trials, 725 couples) we found OS-IUI and IVF/ICSI increased live birth rate compared to expectant management (OR 4.48, 95% CI 2.00 to 10.1; moderate-certainty evidence; OR 4.99, 95 CI 2.07 to 12.04; moderate-certainty evidence), while there was insufficient evidence of a difference between IVF/ICSI and OS-IUI (OR 1.11, 95% CI 0.78 to 1.60; low-certainty evidence).Eleven RCTs including 2564 couples reported on multiple pregnancy. Compared to expectant management/IUI, OS (OR 3.07, 95% CI 1.00 to 9.41; low-certainty evidence) and OS-IUI (OR 3.34 95% CI 1.09 to 10.29; moderate-certainty evidence) increased the odds of multiple pregnancy, and there was insufficient evidence of a difference between IVF/ICSI and expectant management/IUI (OR 2.66, 95% CI 0.68 to 10.43; low-certainty evidence). These findings suggest that if the chance of multiple pregnancy following expectant management or IUI is assumed to be 0.6%, the chance following OS, OS-IUI, and IVF/ICSI would be 0.6% to 5.0%, 0.6% to 5.4%, and 0.4% to 5.5%, respectively.Trial results show insufficient evidence of a difference between IVF/ICSI and OS-IUI for moderate/severe ovarian hyperstimulation syndrome (OHSS) (OR 2.50, 95% CI 0.92 to 6.76; 5 studies; 985 women; moderate-certainty evidence). This suggests that if the chance of moderate/severe OHSS following OS-IUI is assumed to be 1.1%, the chance following IVF/ICSI would be between 1.0% and 7.2%. There is insufficient evidence of differences in live birth between expectant management and the other four interventions (OS, IUI, OS-IUI, and IVF/ICSI). Compared to expectant management/IUI, OS may increase the odds of multiple pregnancy, and OS-IUI probably increases the odds of multiple pregnancy. Evidence on differences between IVF/ICSI and expectant management for multiple pregnancy is insufficient, as is evidence of a difference for moderate or severe OHSS between IVF/ICSI and OS-IUI.

Diminished ovarian reserve (DOR) is associated with reduced euploid rates via preimplantation genetic testing for aneuploidy (PGT-A) independent of age: evidence for concomitant reduction in oocyte quality with quantity

Controversy surrounds whether an age-adjusted reduction in ovarian reserve quantity is accompanied by diminished oocyte quality. We sought to determine whether women with DOR (quantitatively) had lower rates of euploid blastocysts via PGT-A testing, as a proxy for oocyte quality. Retrospective cohort. Results from all day 5 and 6 blastocyst trophectoderm biopsies for PGT-A between 2010-2019 at a single academic were reviewed. Blastocysts graded BB (Gardner) or better are biopsied at our center. Infertility diagnoses were grouped as DOR (assigned by clinicians at initial consultation per Bologna criteria) vs non-DOR infertility. Women >42y were excluded given potential conflation with DOR in this range. Couples without infertility (for example, PGT-A for recurrent pregnancy loss, fertility preservation, or PGT-M) were also excluded. The primary outcome was euploid rate, defined as the number of euploid blastocysts divided by number of blastocysts biopsied per cycle. Generalized linear models were used to account for the clustered nature of the data and control for age of the oocyte. Interaction analyses were performed. A secondary analysis assigned DOR on the basis of age-adjusted mature oocyte (M2) yield, comparing the lowest quartile to the remaining 3/4 by age group. Finally, we compared pregnancy outcomes after euploid single embryo transfer (SET) by DOR status. 8,042 blastocyst PGT-A biopsies from 1,152 women over 1,675 IVF cycles were identified. 225 women (20%) had DOR as infertility diagnosis. Age was higher among DOR women (39.5y vs 37.0y). Euploid rates varied by DOR vs non-DOR (Table). Controlling for age, women with DOR had 24% reduced odds of a biopsied blastocyst being euploid vs non-DOR (Table). Impact of DOR on euploid rates did not differ by age category (interaction p=0.43). When assigning DOR status to women producing the lowest quartile of age-adjusted M2 yield, this relationship remained (Table). No differences were identified in rates of live birth or ongoing pregnancy between patients with and without DOR after SET of a euploid blastocyst (n=944 transfers) (56.8% vs 54.8%, respectively; p=0.88). Blastocysts from women with DOR are less likely to be euploid than those from women without DOR, after adjustment for age. Given the concomitant reduction in euploid rates with quantity of oocytes observed in this study, quantitative ovarian reserve assessments (i.e. follicular machinery) may yield insight into relative ovarian aging.Tabled 1Average euploid rates per cycle, by DOR vs non-DOR; and impact of DOR diagnosis on euploid rates, adjusted for ageClinician-diagnosedLowest 1/4 M2 YieldDORNon-DORDORNon-DOR<3542.8%54.8%45.1%57.5%35-3750.3%50.2%43.5%51.4%38-4027.5%40.8%34.0%38.9%41-4222.4%25.6%28.9%21.9%Total29.0%44.9%38.2%43.2%DOR*aOR 0.76 (95% CI 0.65, 0.90)p<0.01aOR 0.80 (95% CI 0.68, 0.93)p<0.01*Impact of DOR diagnosis on euploid rate, adjusted for age Open table in a new tab

Advanced sperm selection techniques for assisted reproduction.

Advanced sperm selection techniques for assisted reproduction.

Three-dimensional ultrasound diagnosis of T-shaped uterus is associated with adverse pregnancy outcomes after embryo transfer.

Is T-shaped uterine cavity morphology associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst? In this secondary analysis of a prospective cohort study, 648 patients with three-dimensional ultrasound (3D-US) data obtained on the day before embryo transfer were categorized into three groups according to uterine cavity morphology: normal (n = 472), intermediate (n = 166) and T-shaped (n = 10). Quantitative uterine cavity dimensions were used to evaluate uterine cavity morphology. Pregnancy outcomes, including live birth, clinical miscarriage and ectopic pregnancy, were compared among the groups. The prevalence of a T-shaped uterus in this cohort was 1.5%. Uterine cavity morphology was strongly associated with the ratio of interostial distance and isthmic diameter (P < 0.01). Live birth rates were 66.5% for normal, 65.7% for intermediate and 40.0% for T-shaped cavity morphology. Women with a T-shaped uterus had an increased risk of clinical miscarriage (40.0% versus 7.0% for normal and 9.0% for intermediate cavity morphology, P < 0.01) and ectopic pregnancy (10.0% versus 1.1% for normal and 1.9% for intermediate cavity morphology, P = 0.05). When evaluating interostial distance and isthmic diameter ratio to determine pregnancy outcomes, a cut-off value of 2 was noted to have weak predictive value for live birth, but not clinical miscarriage or ectopic pregnancy. T-shaped uterine cavity morphology is associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst. Given the low prevalence of this condition, quantifying the magnitude of risk will require a larger cohort of patients.

Postpartum hemorrhage: not only hypertensive disorders in oocyte donation pregnancies

The aim of the study is to compare the obstetric outcome between single pregnancies obtained by medically-assisted procreation using oocyte donors (MAP-E) versus homologous gametes (MAP-O) and single spontaneous conception pregnancies (SC). This is a retrospective case-control study on pregnancy outcome of consecutive singleton live birth pregnancies from MAP-E between January 2011 and August 2017 referred to Careggi University Hospital, Florence. The control group includes singleton pregnancies from MAP-O and pregnancies from spontaneous conceptions in the same period. The pregnancy outcomes considered were: postpartum hemorrhage (PPH), cesarean section (CS), gestational diabetes mellitus (GDM), hypertensive disorders including preeclampsia (HDP), preterm birth ≤34 weeks (PTB), and small-for-gestational-age (SGA) fetuses. The study group included 290 MAP-E pregnancies that were compared with 290 MAP-O and 870 singleton spontaneous conception pregnancies. The three groups did not show significant differences in maternal traits except for mean age (43.4±2.9 vs. 37.7±2.4 vs. 33.6±5.5, P<0.001), including a higher percentage of patients over 45 years (41.3% vs. 5% vs. 0.8%, P<0.001) and higher incidence of obesity (7.2% vs. 1.7%, P=0.02) in MAP-E than in MAP-O. The risk of HDP is increased in singleton pregnancies by oocyte donation with a significantly increased risk if compared to MAP-O (12% vs. 1%, P<0.001, OR=12.6). The risk of PPH in singleton pregnancies from oocyte donation is higher than in MAP-O (22% vs. 9% P<0.0001, OR=2.87). When we considered severe PPH (blood loss >1000 mL) the risk for MAP-E was higher if compared to MAP-O (OR=2.1, P=0.2) and mostly to SC (OR=14, P<0.005). Compared to SC, MAP-E pregnancies showed increased OR for all the outcomes: CS (78% vs. 30.8%, P<0.001, OR=7.91); GDM (26.1% vs. 10.8%, P<0.001, OR=2.92); HDP (12% vs. 2.2%, P<0.001, OR=5.99); PPH (22% vs. 8.5%, P<0.0001, OR=3.0); SGA (16% vs. 11%, P<0.05, OR=1.16); PTB ≤34 weeks (9.4% vs. 1%, P<0.001, OR=7.94). Most women who undergo MAP-E are in advanced age, representing a high-risk population for obstetric complications, like HPD and PPH, which stands as the main worldwide cause of maternal mortality.

Is maternal weight gain between pregnancies associated with risk of large-for-gestational age birth? Analysis of a UK population-based cohort

ObjectiveMaternal overweight and obesity during pregnancy increases the risk of large-for-gestational age (LGA) birth and childhood obesity. We aimed to investigate the association between maternal weight change between subsequent pregnancies...

Time-lapse systems for embryo incubation and assessment in assisted reproduction.

Time-lapse systems for embryo incubation and assessment in assisted reproduction.

Comparison of daily vaginal progesterone gel plus weekly intramuscular progesterone with daily intramuscular progesterone for luteal phase support in single, autologous euploid frozen-thawed embryo transfers

To compare outcomes between daily intramuscular progesterone (IMP) and daily vaginal progesterone (VP) gel plus weekly intramuscular hydroxyprogesterone caproate (IMHPC) for luteal phase support (LPS) in single, autologous euploid frozen-thawed blastocyst transfers (FBTs) following artificial endometrial preparation (EP). The retrospective cohort study included 767 single, autologous FBTs from 731 patients between January 2015 and March 2018. LPS was performed either with IMP (100mg/day) or with VP gel (90mg, twice daily) plus IMHPC (250mg/week). Oral estrogen was prescribed in combination of both regimes. Oral estrogen was discontinued following the visualization of fetal cardiac activity on ultrasound and progesterone at 10weeks of gestation. The primary outcome was live birth rate. The secondary outcomes included implantation, clinical pregnancy, and multiple pregnancy rates. Patient characteristics did not differ in LPS regimes. Of 767 FBTs, 608 had IMP (100mg/day) for LPS and 159 had VP gel (90mg, twice daily) plus IMHPC (250mg/week) for LPS. The live birth rate was 51.8% and 50.3%, respectively (p = 0.737, OR 0.94, 95%CI 0.66-1.33). The implantation rate was 62.7% and 64.2%, respectively (p = 0.730, OR 1.06, 95%CI 0.74-1.53). The clinical pregnancy rates were also similar in both groups (59.5% vs. 61.6%, respectively, p = 0.631, OR 1.09, 95%CI 0.76-1.56). We did not observe significant differences in the rates of live birth, implantation, and clinical pregnancy between daily IMP and daily VP gel plus weekly IMHPC for LPS in single, autologous euploid FBTs after artificial EP.

Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis

To investigate the rate of sperm DNA fragmentation in male partners of women with recurrent pregnancy loss and fertile control women. Systematic review and meta-analysis. Not applicable. A total of 579 male partners of women with recurrent pregnancy loss and 434 male partners fertile control women. Prospective studies were identified through a Pubmed search. Recurrent pregnancy loss was defined as two or more previous pregnancy losses. Fertile control women had a history of a live birth or ongoing pregnancy. The primary outcome was the rate of sperm DNA fragmentation. The summary measures were reported as mean difference with 95% confidence interval (CI). Fifteen prospective studies were included in a qualitative review. Pooled data from 13 studies with sufficient data for meta-analysis suggest that male partners of women with a history of recurrent pregnancy loss have a significantly higher rate of sperm DNA fragmentation compared to the partners of fertile control women: mean difference 11.91, 95% CI 4.97-18.86. These findings support an association between sperm DNA fragmentation and recurrent pregnancy loss. However, given the significant heterogeneity between studies and lack of prospective pregnancy outcome data, further large prospective studies are needed.

Screening hysteroscopy in subfertile women and women undergoing assisted reproduction.

Screening hysteroscopy in infertile women with unexplained infertility, or prior to intrauterine insemination (IUI) or in vitro fertilisation (IVF) may reveal intrauterine pathology that may not be detected by routine transvaginal ultrasound. Hysteroscopy, whether purely diagnostic or operative may improve reproductive outcomes. To assess the effectiveness and safety of screening hysteroscopy in subfertile women undergoing evaluation for infertility, and subfertile women undergoing IUI or IVF. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL CRSO, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (September 2018). We searched reference lists of relevant articles and handsearched relevant conference proceedings. Randomised controlled trials comparing screening hysteroscopy versus no intervention in subfertile women wishing to conceive spontaneously, or before undergoing IUI or IVF. We independently screened studies, extracted data, and assessed the risk of bias. The primary outcomes were live birth rate and complications following hysteroscopy. We analysed data using risk ratio (RR) and a fixed-effect model. We assessed the quality of the evidence by using GRADE criteria. We retrieved 11 studies. We included one trial that evaluated screening hysteroscopy versus no hysteroscopy, in women with unexplained subfertility, who were trying to conceive spontaneously. We are uncertain whether ongoing pregnancy rate improves following a screening hysteroscopy in women with at least two years of unexplained subfertility (RR 4.30, 95% CI 2.29 to 8.07; 1 RCT; participants = 200; very low-quality evidence). For a typical clinic with a 10% ongoing pregnancy rate without hysteroscopy, performing a screening hysteroscopy would be expected to result in ongoing pregnancy rates between 23% and 81%. The included study reported no adverse events in either treatment arm. We are uncertain whether clinical pregnancy rate is improved (RR 3.80, 95% CI 2.31 to 6.24; 1 RCT; participants = 200; very low-quality evidence), or miscarriage rate increases (RR 2.80, 95% CI 1.05 to 7.48; 1 RCT; participants = 200; very low-quality evidence), following screening hysteroscopy in women with at least two years of unexplained subfertility.We included ten trials that included 1836 women who had a screening hysteroscopy and 1914 women who had no hysteroscopy prior to IVF. Main limitations in the quality of evidence were inadequate reporting of study methods and higher statistical heterogeneity. Eight of the ten trials had unclear risk of bias for allocation concealment.Performing a screening hysteroscopy before IVF may increase live birth rate (RR 1.26, 95% CI 1.11 to 1.43; 6 RCTs; participants = 2745; I² = 69 %; low-quality evidence). For a typical clinic with a 22% live birth rate, performing a screening hysteroscopy would be expected to result in live birth rates between 25% and 32%. However, sensitivity analysis done by pooling results from trials at low risk of bias showed no increase in live birth rate following a screening hysteroscopy (RR 0.99, 95% CI 0.82 to 1.18; 2 RCTs; participants = 1452; I² = 0%).Only four trials reported complications following hysteroscopy; of these, three trials recorded no events in either group. We are uncertain whether a screening hysteroscopy is associated with higher adverse events (Peto odds ratio 7.47, 95% CI 0.15 to 376.42; 4 RCTs; participants = 1872; I² = not applicable; very low-quality evidence).Performing a screening hysteroscopy before IVF may increase clinical pregnancy rate (RR 1.32, 95% CI 1.20 to 1.45; 10 RCTs; participants = 3750; I² = 49%; low-quality evidence). For a typical clinic with a 28% clinical pregnancy rate, performing a screening hysteroscopy would be expected to result in clinical pregnancy rates between 33% and 40%.There may be little or no difference in miscarriage rate following screening hysteroscopy (RR 1.01, 95% CI 0.67 to 1.50; 3 RCTs; participants = 1669; I² = 0%; low-quality evidence).We found no trials that compared a screening hysteroscopy versus no hysteroscopy before IUI. At present, there is no high-quality evidence to support the routine use of hysteroscopy as a screening tool in the general population of subfertile women with a normal ultrasound or hysterosalpingogram in the basic fertility work-up for improving reproductive success rates.In women undergoing IVF, low-quality evidence, including all of the studies reporting these outcomes, suggests that performing a screening hysteroscopy before IVF may increase live birth and clinical pregnancy rates. However, pooled results from the only two trials with a low risk of bias did not show a benefit of screening hysteroscopy before IVF.Since the studies showing an effect are those with unclear allocation concealment, we are uncertain whether a routine screening hysteroscopy increases live birth and clinical pregnancy, be it for all women, or those with two or more failed IVF attempts. There is insufficient data to draw conclusions about the safety of screening hysteroscopy.

Mental Disorders and Suicide Attempts in the Pregnancy and Postpartum Periods Compared with Non-Pregnancy: A Population-Based Study.

To compare the rate of mental disorders (i.e., mood and anxiety, substance use, psychotic disorders) and suicide attempts within the same group of women across the pre-pregnancy, pregnancy, and postpartum periods, and between this perinatal cohort and a non-perinatal reference group. Data were from an administrative repository of residents in Manitoba, Canada. The perinatal cohort consisted of women aged 18 to 45 years who experienced >1 live birth pregnancy between 2011 and 2014 (n = 45,362). Pre-pregnancy, pregnancy, and postpartum periods were defined over consecutive 40-week intervals. The non-perinatal cohort consisted of age-matched women with no pregnancies during the same period (n = 139,705). A reference 40-week interval was defined from the individual's birthdate in the year they entered the cohort. Rate ratios of diagnosed mental disorders were adjusted (aRR) for demographic factors, parity, and mental health history. Within the perinatal cohort, pregnancy was associated with a lower rate of diagnosed mood or anxiety disorder, substance use disorder, and suicide attempt relative to pre-pregnancy (aRR range, 0.22-0.82). Pregnancy also had lower rates of all outcomes compared with the postpartum period (aRR, 0.44-0.87). Postpartum had a higher rate of psychotic disorder compared with pre-pregnancy (aRR, 1.61; 95% CI, 1.17-2.21), but a lower rate of mood or anxiety disorder and suicide attempt. Compared with non-perinatal women, pregnancy was associated with lower rates of all outcomes (aRR range, 0.25-0.87). Compared with a non-perinatal period, the rate of a diagnosed mental disorder is lower during pregnancy but begins to rise in the postpartum period, highlighting an important period for early identification and rapid access to intervention.