Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH): recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35-40 years: A German database study.

This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation (OS) during assisted reproductive technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.2, 31.6] vs. 27.8% [26.5, 29.2]) and live birth (20.3% [18.7, 21.8] vs. 18.0% [16.6, 19.4]) rates were observed with r-hFSH:r-hLH versus r-hFSH alone. The treatment effect was consistently higher for r-hFSH:r-hLH compared with r-hFSH alone in terms of clinical pregnancy (relative risk [RR] 1.16 [1.05, 1.26]) and live birth (RR 1.16 [1.02, 1.31]) in a post-hoc analysis of women with 5-14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of r-hFSH:r-hLH for OS in women aged 35-40 years with normal ovarian reserve.

Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: A global perspective.

Considerable costs are associated with infertility treatment, but little evidence is available on the main drivers of treatment costs. This cost analysis investigated key costs for treatment with assisted reproductive technology (ART) and the proportion of costs attributed to the acquisition of recombinant human follicle-stimulating hormone (r-hFSH) alfa originator for one fresh embryo transfer (ET) leading to a live birth in Spain, Norway, the UK, Germany, Denmark, South Korea, Australia, and New Zealand. The total costs for one ART cycle with a fresh ET leading to a live birth varied between countries (€4108-€12,314). Costs for pregnancy and live birth were the major contributors in European countries, and the costs of oocyte retrieval, monitoring during ovarian stimulation, pregnancy, and live birth were the top contributors in the Asia-Pacific countries, included in this analysis. Acquisition costs for r-hFSH alfa originator contributed to only 5%-17% of the total costs of one ART cycle with one fresh ET leading to a live birth.

Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group.

Factors associated with embryo splitting and clinical outcome of monozygotic twins in pregnancies after IVF and ICSI.

STUDY QUESTION: What factors are associated with monozygotic twins (MZT) after autologous IVF/ICSI with fresh and frozen/thawed single embryo transfer (SET) and what is the outcome of MZT? SUMMARY ANSWER: Factors associated with increased MZT were blastocyst transfer and elective single embryo transfer (eSET), with MZT showing a lower gestational age at birth and neonatal weight but higher perinatal mortality only after fresh transfer. WHAT IS KNOWN ALREADY: ART is associated with an increased incidence of MZT, which carries higher perinatal mortality. However, risk factors associated with MZT are still controversial. STUDY DESIGN SIZE DURATION: A population-based retrospective analysis of data extracted from ART cycles reported to the Latin American Registry of ART between January 2012 and December 2016 was used in order to study the frequency and outcome of MZT after SET. PARTICIPANTS/MATERIAL SETTING METHODS: In total, 2925 clinical pregnancies obtained after autologous IVF/ICSI with fresh SET were used to study biomedical factors possibly associated with MZT, such as maternal age, type of insemination, use of assisted hatching, stage of embryo development at transfer, elective or non-elective SET and preimplantation genetic testing. Another group of 3085 clinical pregnancies obtained after SET of frozen-thawed embryo transfer (FET) was also used to study the possible association between embryo freezing and MZT. Only pregnancies with complete follow-up until birth were included in this analysis. The diagnosis of MZT was established by transvaginal ultrasound performed at 6­8 weeks of amenorrhea. The rate of MZT for each potential risk factor was obtained and a multivariable logistic regression was performed in order to account for the above-mentioned factors. Pregnancies were followed until birth and the early neonatal period in order to assess the rate of miscarriage and stillbirths, gestational age at birth, neonatal weight and early neonatal mortality. MAIN RESULTS AND ROLE OF CHANCE: There were 76 MZT out of 2925 clinical pregnancies with fresh SET (2.6%) and 69 MZT out of 3085 clinical pregnancies after FET (2.2%) (odds ratio (OR) = 0.85, 95% CI 0.61­1.19). A statistically significantly increase in MZT rate was observed with blastocyst compared with cleavage stage ET (3.4 versus 2.0%, respectively; OR = 1.70, 95% CI 1.05­2.76). When confounding variables were considered, eSET was also significantly associated with an increase in the odds of MZT (OR = 1.74, 95% CI 1.04­2.92). Overall perinatal mortality was higher in MZT compared with singletons, but this rise was only significant after fresh ET. LIMITATIONS REASONS FOR CAUTION: Limitations of the current study result from the fact that MZT were diagnosed with ultrasound performed at 6­8 weeks of amenorrhea; therefore, spontaneous embryo reductions taking place earlier were missed. WIDER IMPLICATIONS OF THE FINDINGS: Reproductive health providers must inform their patients that blastocyst transfer and eSET of fresh embryos are associated with a statistically significantly increase in the odds of MZT and that perinatal mortality after fresh ET is significantly higher in MZT than in singletons. STUDY FUNDING/COMPETING INTERESTS: The Latin American Registry of ART receives direct funding from Ferring Pharmaceuticals, but no specific funding was received to undertake this study. None of the authors declare conflict of interest.

[Premature labor with intact membranes: microbiology of the amniotic fluid and lower genital tract and its relation with maternal and neonatal outcome]. / Parto prematuro con membranas intactas: microbiología del líquido amniótico y tracto genital inferior y su relación con los resultados materno neonatales.

BACKGROUND: The prevalence of idiopathic spontaneous premature labor or without an evident clinical cause, has not been reduced with tocolytic treatments, suggesting that premature labor has multiple causes and infections play a not well-defined role. AIM: To perform microbiological studies of the amniotic fluid and of the lower genital tract in women with idiopathic premature labor and intact membranes, relating these findings with maternal and neonatal outcomes. PATIENTS AND METHODS: Women with pregnancies between 24 and 34 weeks, with premature labor and without an evident clinical cause were enrolled. Amniotic fluid and genital tract samples were obtained for traditional microbiological cultures. This information was related with delivery events and neonatal outcome. RESULTS: Sixty-three patients were included. The overall frequency of microbial invasion of amniotic cavity was 23.8% and of cervical or vaginal infection was 63.5% (in 39.7% there was only cervical or vaginal infection without involvement of the amniotic sac). Absence of infection was documented in 36.5% of women. Compared to patients without infection, women with microbial invasion of amniotic cavity had a higher rate of prematurity (73.3% p < 0.05), a higher rate of prematurity of less than 34 weeks (60% p < 0.01), a higher frequency of preterm rupture of membranes (40% p < 0.001), a shorter admission-to-delivery interval (median 3.0 days p < 0.01) and lower gestational age at delivery (median 33 weeks p < 0.01). Clinical chorioamnionitis and endometritis (20% p < 0.01) was observed only in patients with amniotic cavity infections. Severe asphyxia (26.7% p < 0.05) and neonatal admission to Intensive Care Units (46.7% p < 0.05) were more frequent and neonatal weight was less in the offspring of women with microbial invasion of amniotic cavity (2020 g median p < 0.01). CONCLUSIONS: In preterm labor with intact membranes, intraamniotic infection is the most frequent cause of prematurity and is associated with a higher prevalence of maternal and neonatal problems.