OBJECTIVE: To investigate whether the risk for post-partum cardiovascular diseases (CVD) is driven by gestational diabetes (GDM), by GDM-related risk factors and/or by pre-gestational (Pre-GD) or post-gestational diabetes (Post-GD).
METHODS: Women delivering in Tuscany, Italy in years 2010-2012 (n = 74,720), were identified from certificates of care at delivery and further identified as affected with GDM, Pre-GD or Post-GD through regional administrative databases. Women with GDM, Pre-GD or Post-GD were retrospectively evaluated for risk of post-partum hospitalizations for CVD (myocardial infarction or stroke; n = 728) across years 2013-2021, comparing women with different forms of diabetes to those without diabetes. Risk of CVD was assessed as odds ratio (OR 95% CI), after logistic multivariate models, considering all recorded pre-gestational characteristics as covariates.
RESULTS: The adjusted OR (aOR) for post-partum CVD hospitalizations was not significantly related to GDM itself (aOR: 0.85; 0.64-1.12; p = ns), but increased in women with Pre-GD (aOR: 2.02; 1.09-3.71; p = 0.024) and Post-GD, associated or not to prior GDM (aOR; 4.21; 2.45-7.23 and respectively aOR: 3.80; 2.38-6.05; p < 0.0001 for both). In presence of pre-pregnancy maternal obesity (BMI ≥ 30 kg/m2) the aOR of CVD approximatively doubled (aOR: 1.90; 1.51-2.40); p < 0.0001, independently of GDM and of Post-GD. The adjusted risk of CVD was lower among employed women (aOR: 0.83; 0.70-0.99); p = 0.04 and significantly higher in presence of poorer education levels (aOR: 1.32; 1.11-1.57); p < 0.0001.
CONCLUSIONS: In this population the risk of post-partum CVD was driven by Pre- and Post-GD, not by GDM alone. Pre-gestational obesity represented a major independent risk factor for post-partum CVD.

OBJECTIVE: How does a gonadotrophin-releasing hormone (GnRH) agonist versus a GnRH antagonist protocol affect ovarian response when using an individualized fixed daily dose of follitropin delta for ovarian stimulation?
CONCLUSIONS: The BEYOND trial data demonstrate thatindividualized fixed-dose follitropin delta is effective when used in a GnRH agonist protocol, compared with a GnRH antagonist protocol, in women with anti-Müllerian hormone (AMH) ≤35 pmol/l and no increased risk of ovarian hyperstimulation syndrome (OHSS).
BACKGROUND: The efficacy and safety of an individualized fixed daily dose of follitropin delta (based on body weight and AMH) have been established in randomized controlled trials (RCTs) using a GnRH antagonist protocol. Preliminary study data indicate that individualized follitropin delta is also efficacious in a GnRH agonist protocol (RAINBOW trial, NCT03564509). There are no prospective comparative data using individualized follitropin delta for ovarian stimulation in a GnRH agonist versus a GnRH antagonist protocol.
METHODS: This is the first randomized, controlled, open-label, multi-centre trial exploring efficacy and safety of individualized follitropin delta dosing in a GnRH agonist versus a GnRH antagonist protocol in participants undergoing their first ovarian stimulation cycle for IVF/ICSI. A total of 437 participants were randomized centrally and stratified by centre and age. The primary endpoint was the number of oocytes retrieved. Secondary endpoints included ongoing pregnancy rates, adverse drug reactions (including OHSS), live births, and neonatal outcomes.
METHODS: Participants (18-40 years; AMH ≤35 pmol/l) were enrolled at specialist reproductive health clinics in Austria, Denmark, Israel, Italy, the Netherlands, Norway, and Switzerland. The mean number of oocytes retrieved was compared between the GnRH agonist and antagonist protocols using a negative binomial regression model with age and AMH at screening as factors. Analyses were based on all randomized subjects, using a multiple imputation method for randomized subjects withdrawing before the start of stimulation.
RESULTS: Of the 437 randomized subjects, 221 were randomized to the GnRH agonist, and 216 were randomized to the GnRH antagonist protocol. The participants had a mean age of 32.3 ± 4.3 years and a mean serum AMH of 16.6 ± 7.8 pmol/l. A total of 202 and 204 participants started ovarian stimulation with follitropin delta in the GnRH agonist and antagonist groups, respectively. The mean number of oocytes retrieved was statistically significantly higher in the agonist group (11.1 ± 5.9) versus the antagonist group (9.6 ± 5.5), with an estimated mean difference of 1.31 oocytes (95% CI: 0.22; 2.40, P = 0.0185). The difference in number of oocytes retrieved was influenced by the patients\' age and ovarian reserve, with a greater difference observed in patients aged <35 years and in patients with high ovarian reserve (AMH >15 pmol/l). Both the GnRH agonist and antagonist groups had a similar proportion of cycle cancellations (2.0% [4/202] versus 3.4% [7/204]) and fresh blastocyst transfer cancellations (13.4% [27/202] versus 14.7% [30/204]). The estimated ongoing pregnancy rate per started cycle was numerically higher in the GnRH agonist group (36.9% versus 29.1%; difference: 7.74% [95% CI: -1.49; 16.97, P = 0.1002]). The most commonly reported adverse events (≥1% in either group; headache, OHSS, nausea, pelvic pain, or discomfort and abdominal pain) were similar in both groups. The incidence of early moderate/severe OHSS was low (1.5% for the agonist group versus 2.5% for antagonist groups). Estimated live birth rates per started cycle were 35.8% and 28.7% in the GnRH agonist and antagonist groups, respectively (treatment difference 7.15%; 95% CI: -2.02; 16.31; P = 0.1265). The two treatment groups were comparable with respect to neonatal health data for singletons and twins and for incidence of congenital malformations (2.7% and 3.3% for the GnRH agonist versus antagonist groups, respectively).
CONCLUSIONS: All participants had AMH ≤35 pmol/l and were ≤40 years old. Clinicians should remain cautious when using a GnRH agonist protocol in patients with AMH >35 pmol/l (i.e. those with an increased OHSS risk). The incidence of OHSS in the GnRH antagonist group may have been lower if a GnRH agonist trigger had been allowed. Outcomes of transfers with cryopreserved blastocysts were not followed up, therefore the cumulative live birth rates and neonatal outcomes after cryotransfer are unknown.
CONCLUSIONS: In women with AMH ≤35 pmol/l, an individualized fixed daily dose of follitropin delta resulted in a significantly higher number of oocytes retrieved when used in a GnRH agonist protocol compared with a GnRH antagonist protocol, with no additional safety signals observed and no additional risk of OHSS. Live birth rates following ovarian stimulation with individualized follitropin delta were not statistically different between the GnRH protocols; however, the trial was not powered to assess this endpoint. There were no safety concerns with respect to neonatal health after ovarian stimulation with follitropin delta in either protocol.
BACKGROUND: The trial was funded by Ferring Pharmaceuticals. EE, EP, and MS have no competing interests. AP has received research support from Ferring, and Gedeon Richter, and honoraria or consultation fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, Merck A/S. BC has received consulting fees from Ferring and Merck, and his department received fees from Ferring to cover the costs of patient enrolment. MBS has received support to attend meetings and/or travel from Ferring, and was a board member for FertiPROTEKT e.V. until 2023. JS has received honoraria or consultation fees from Ferring and Merck, and support for attending meetings and/or travel from Ferring, Merck, and GoodLife. TS has received support/travel expenses from Ferring for attending a congress meeting, and participated in an advisory board for Merck. YS has received grants/research support from Ferring and support to attend a professional society congress meeting from Merck. RL and PP are employees of Ferring Pharmaceuticals. PP is a BOD member of PharmaBiome and owns stocks of Takeda Pharmaceuticals.
BACKGROUND: ClinicalTrials.gov identifier NCT03809429; EudraCT Number 2017-002783-40.
UNASSIGNED: 7 April 2019.
UNASSIGNED: 2 May 2019.

Cultural practices help constitute a \'normal\' way of life within a specific community and set the standard that members of the community are expected to adhere to. Some of these practices may have a short- and long-term influence on young people in ways supportive of teenage motherhood. This study explored cultural practices and beliefs in a study area in Ghana that encourage teenage girls into motherhood unintendedly. An exploratory design was used. Thirty teenage mothers and twenty-two opinion leaders participated in fieldwork conducted between October 2018 and February 2019. Data were analysed using an inductive approach. Four themes became apparent: fear of being cursed for having an abortion; sleeping arrangements; funerals and wakes; and practices of cohabitation in the study area. Cultural practices contribute to teenage motherhood in the Adaklu District of Ghana. Programmes, interventions and policies should be designed to take into consideration the needs, contexts, and backgrounds of teenagers. Future programmes to enhance teenagers ability to avoid teenage pregnancy and motherhood should consider factors such as the family, the person, the community, institutions, and national and international influences.

UNASSIGNED: The efficiency of ovarian tissue transplantation (OTT) was established in terms of ovarian function recovery (95% of cases), number of live births (over 200 worldwide to date) and induction of puberty. Unfortunately, the lack of international registries and the fact that many centers have not yet reported their outcomes, lead to poor knowledge of the exact fertility data. The aim of the study is to describe our experience with OTT to restore ovarian function and fertility.
UNASSIGNED: This study was designed as a single-center, observational, retrospective, cohort study that includes women who underwent OTT between December 2012 and June 2023 at our center. After approval by the oncologist/hematologist, a small fragment of ovarian tissue was thawed and analyzed to detect the presence of micrometastases before OTT. Thawed ovarian tissue was grafted laparoscopically at multiple sites, including the remaining ovary and pelvic side wall (orthotopic transplantation) and/or abdominal wall (heterotopic transplantation). After OTT, ovarian function was monitored by hormonal assay, ultrasound and color Doppler at approximately 4-week intervals.
UNASSIGNED: Between December 2012 and June 2023, 30 women performed OTT. Prior to OTT, immunohistochemical and molecular analyses revealed no micrometastases in all thawed ovarian tissue samples. In our series of 30 women, 20 of women were on premature ovarian insufficiency (POI), and the remaining ten cases still had oligomenorrhea and difficulty getting pregnant. Among the women with POI before OTT and at least 6 months follow-up, recovery of endocrine function was observed in all but one woman who underwent orthotopic transplantation (13 of 14 cases), in one out of two women who underwent both orthotopic and heterotopic transplantation (1 of 2 cases) and in all women who underwent heterotopic transplantation (4 of 4 cases). Women who underwent OTT to enhance fertility had no alterations in menstrual cycle and hormonal levels. In total, ten pregnancies were obtained in 25 women, resulting in four live births, two ongoing pregnancies and four spontaneous abortions.
UNASSIGNED: Our data can help patients and physicians in their discussions and decisions about the need and possibilities of preserving fertility.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women.
METHODS: A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI).
RESULTS: A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved.
CONCLUSIONS: This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes.

Early preeclampsia is associated with significant placental hypoperfusion. We explore the diagnostic value of placental diffusion-derived vessel density (DDVD), a biomarker derived from diffusion-weighted magnetic resonance imaging, which measures in vivo vessel microperfusion, in the differential diagnosis of normal and early preeclampsia pregnancies.
This was a prospective study involving 29 controls and 17 singleton pregnancies affected by early preeclampsia. Nineteen pregnancies from 28 to 34 weeks of gestational age were included from the normal group for a comparison with the early preeclampsia group. Using a 3.0 T magnetic resonance imaging scanner, diffusion-weighted images were obtained with the diffusion weighting b values of 0, 20, and 40 s/mm2. DDVDmean was the mean of DDVDb0b20 and DDVDb0b40, while DDVDb0b20 and DDVDb0b40 refer to the diffusion-derived vessel density values computed from b=0 and 20 s/mm2 images, and from b=0 and 40 s/mm2 images, respectively. The correlation between DDVDmean and gestational age was examined using a linear regression model. The area under the curve of the DDVDmean for early preeclampsia pregnancies detection was calculated by the receiver operating characteristic analysis.
As gestational age increased, DDVDmean linearly decreased. DDVDmean was significantly decreased in the early preeclampsia pregnancies compared with the normal pregnancies (52.72±46.73 versus 213.34±93.50 au/pixel; P<0.001). The area under the curve (DDVDmean) for discriminating between normal and early preeclampsia pregnancies regardless of fetal growth restriction was 0.954, and the area under the curve was 1.000 when early preeclampsia pregnancies without fetal growth restriction were excluded.
DDVDmean, an in vivo vessel microperfusion measure, allowed total separation of normal and early preeclampsia pregnancies.

Low-dose aspirin treatment reduces the risk of preeclampsia among high-risk pregnant women. Internationally, several first-trimester risk-calculation methods are applied.
This study aimed to assess the costs and benefits of different first-trimester preeclampsia risk estimation algorithms: EXPECT (an algorithmic prediction model based on maternal characteristics), National Institute for Health and Care Excellence (a checklist of risk factors), and the Fetal Medicine Foundation (a prediction model using additional uterine artery Doppler measurement and laboratory testing) models, coupled with low-dose aspirin treatment, in comparison with no risk assessment.
We constructed a decision analytical model estimating the number of cases of preeclampsia with each strategy and the costs of risk assessment for preeclampsia and early aspirin treatment, expressed in euros (€) in a hypothetical population of 100,000 women. We performed 1-way sensitivity analyses to assess the impact of adherence rates on model outcomes.
Application of the EXPECT, National Institute for Health and Care Excellence, and Fetal Medicine Foundation models results in respectively 1.98%, 2.55%, and 1.90% of the women developing preeclampsia, as opposed to 3.00% of women in the case of no risk assessment. Overall, the net financial benefits of the EXPECT, National Institute for Health and Care Excellence, and Fetal Medicine Foundation models relative to no risk assessment are €144, €43, and €38 per patient, respectively. The respective percentages of women receiving aspirin treatment are 18.6%, 10.2%, and 6.0% for the 3 risk assessment methods.
The EXPECT and Fetal Medicine Foundation model are comparable with regard to numbers of prevented preeclampsia cases, and both are superior to the National Institute for Health and Care Excellence model and to no risk assessment. EXPECT is less resource-demanding and results in the highest cost savings, but also requires the highest number of women to be treated with aspirin. When deciding which strategy is preferable, cost savings and easier use have to be weighed against the degree of overtreatment, although low-dose aspirin has no clear disadvantages during pregnancy.

The incidence of ectopic pregnancy (EP) is 1.3-2.4%. Suspicion of EP starts after a positive serum pregnancy test and failure to visualize the intrauterine gestational sac (GS) by transvaginal sonography (TVS). About 88% of tubal EPs are diagnosed by absent intrauterine GS and the presence of an adnexal mass during TVS. Medical treatment of EP using methotrexate (MTX) is cost-effective with a similar success rate to surgical treatment. The presence of fetal heart beats, β-human chorionic gonadotropin >5000 mIU/mL, and EP size >4 cm are relative contraindications for using MTX in the treatment of EP.

Can early pregnancies be accurately and cost-effectively diagnosed and managed using a new medical computerized tool?
Compared to the standard clinical approach, retrospective implementation of the new medical software in a gynaecological emergency unit was correlated with more accurate diagnosis and more cost-effective management.
Early pregnancy complications are responsible for a large percentage of consultations, mostly in emergency units, with guidelines becoming complex and poorly known/misunderstood by practitioners.
A total of 780 gynaecological emergency consultations (446 patients), recorded between November 2018 and June 2019 in a tertiary university hospital, were retrospectively encoded in a new medical computerized tool. The inclusion criteria were a positive hCG test result, ultrasonographical visualization of gestational sac, and/or embryo corresponding to a gestational age of 14 weeks or less. Diagnosis and management suggested by the new computerized tool are named eDiagnoses, while those provided by a gynaecologist member of the emergency department staff are called medDiagnoses.
Usability was the primary endpoint, with accuracy and cost reduction, respectively, as secondary and tertiary endpoints. Identical eDiagnoses/medDiagnoses were considered as accurate. During follow-up visits, if the updated eDiagnoses and medDiagnoses became both identical to a previously discrepant eDiagnosis or medDiagnosis, this previous eDiagnosis or medDiagnosis was also considered as correct. Four double-blinded experts reviewed persistent discrepancies, determining the accurate diagnoses. eDiagnoses/medDiagnoses accuracies were compared using McNemar\'s Chi square test, sensitivity, specificity, and predictive values.
Only 1 (0.1%) from 780 registered medical records lacked data for full encoding. Out of the 779 remaining consultations, 675 eDiagnoses were identical to the medDiagnoses (86.6%) and 104 were discrepant (13.4%). From these 104, 60 reached an agreement during follow-up consultations, with 59 medDiagnoses ultimately changing into the initial eDiagnoses (98%) and only one discrepant eDiagnosis turning later into the initial medDiagnosis (2%). Finally, 24 remained discrepant at all subsequent checks and 20 were not re-evaluated. Out of these 44, the majority of experts agreed on 38 eDiagnoses (86%) and 5 medDiagnoses (11%, including four twin pregnancies whose twinness was the only discrepancy). No majority was reached for one discrepant eDiagnosis/medDiagnosis (2%). In total, the accuracy of eDiagnoses was 99.1% (675 + 59 + 38 = 772 eDiagnoses out of 779), versus 87.4% (675 + 1 + 5 = 681) for medDiagnoses (P < 0.0001). Calculating all basic costs of extra consultations, extra-medications, extra-surgeries, and extra-hospitalizations induced by incorrect medDiagnoses versus eDiagnoses, the new medical computerized tool would have saved 3623.75 Euros per month. Retrospectively, the medical computerized tool was usable in almost all the recorded cases (99.9%), globally more accurate (99.1% versus 87.4%), and for all diagnoses except twinning reports, and it was more cost-effective than the standard clinical approach.
The retrospective study design is a limitation. Some observed improvements with the medical software could derive from the encoding by a rested and/or more experienced physician who had a better ultrasound interpretation. This software cannot replace clinical and ultrasonographical skills but may improve the compliance to published guidelines.
This medical computerized tool is improving. A new version considers diagnosis and management of multiple pregnancies with their specificities (potentially multiple locations, chorioamnionicity). Prospective evaluations will be required. Further developmental steps are planned, including software incorporation into ultrasound devices and integration of previously published predictive/prognostic factors (e.g. serum progesterone, corpus luteum scoring).
No external funding was obtained for this study. F.B. and D.G. created the new medical software.
NCT03993015.

Bariatric surgery has a favorable effect on fertility in women. However, due to a lack of data regarding children\'s outcomes, the ideal time for conception following bariatric surgery is unknown. Current guidelines advise avoiding pregnancy during the initial weight loss phase (12-24 months after surgery) as there may be potential risks to offspring. Thus, we aimed to analyze health outcomes in children born to mothers who had undergone bariatric surgery. The surgery-to-delivery interval was studied.
A nationwide registry belonging to the Austrian health insurance funds and containing health-related data claims was searched. Data for all women who had bariatric surgery in Austria between 01/2010 and 12/2018 were analyzed. A total of 1057 women gave birth to 1369 children. The offspring\'s data were analyzed for medical health claims based on International Classification of Diseases (ICD) codes and number of days hospitalized. Three different surgery-to-delivery intervals were assessed: 12, 18, and 24 months.
Overall, 421 deliveries (31%) were observed in the first 2 years after surgery. Of these, 70 births (5%) occurred within 12 months after surgery. The median time from surgery to delivery was 34 months. Overall, there were no differences noted in frequency of hospitalization and diagnoses leading to hospitalization in the first year of life, regardless of the surgery-to-delivery interval.
Pregnancies in the first 24 months after bariatric surgery were common. Importantly, the surgery-to-delivery interval had no significant impact on the health outcome of the children.