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This trial compared letrozole with gonadotropin or clomiphene in women with unexplained infertility. Letrozole resulted in a significantly lower frequency of multiple gestation, but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. Therapeutic options for couples with unexplained infertility include assisted reproductive technologies, such as in vitro fertilization (IVF) and embryo transfer, and empirical ovarian stimulation combined with intrauterine insemination. The high cost and limited insurance coverage of IVF in all but a few locales in the United States make it an unattainable option for most infertile couples. 1 Empirical ovarian stimulation has been thought to promote childbearing by increasing the number of ova ovulated, as well as possibly by enhancing implantation, placentation, or both through hormonal effects on the endometrium. 2 – 4 However, empirical ovarian stimulation (with clomiphene or particularly with gonadotropin) is . . .

Objectives To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child.Design Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial.Setting 17 centres in the Netherlands.Participants Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility.Interventions Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation.Main outcome measures The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortalityResults 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation).Conclusions In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates.Trial registration Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.

Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24·7% (61/247) in the progesterone group and 19·4% (48/247) in the placebo group (odds ratio [OR] 1·36, 95% CI 0·89–2·09; p=0·16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1·16, 95% CI 0·89–1·51). Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. Chief Scientist Office of the Scottish Government Health Directorate.

Objective Multiple pregnancies carry an increased risk of maternal and perinatal complications, notably prematurity. Few studies have evaluated the risk factors for preterm births in multiple pregnancies within the Thai population. This study aims to ascertain maternal and perinatal outcomes and identify factors linked to preterm births in multiple pregnancies. Methods This study was carried out at Khon Kaen University, Faculty of Medicine, Department of Obstetrics and Gynecology in Thailand. We reviewed the medical records of women with multiple pregnancies who delivered at a gestational age of more than 20 weeks between January 1, 2012 and December 31, 2021. We excluded patients with incomplete data or those for whom data were missing. Results Out of 21,400 pregnancies, 427 were multiple pregnancies, constituting approximately 1.99%. Over the ten-year period, 269 multiple pregnancies (65.1%) resulted in preterm births. Of these, 173 (64.3%) were monochorionic twins, and 96 (35.7%) were dichorionic twins. Monochorionic twins had a notably higher rate of preterm delivery (AOR, 2.06; 95%CI 1.29—3.30). Vaginal delivery was observed in 7.9% of the cases, while cesarean sections were performed for both twins in 91.5% of cases. In 0.5% of the cases, only the second twin was delivered by cesarean section. In terms of neonatal outcomes, 160 infants (19.4%) weighed less than 1,500 g at birth, and there were 78 perinatal deaths (9.4%). Birth asphyxia was noted in 97 cases (20.2%) among monochorionic twins and in 28 cases (8.1%) for dichorionic twins. Conclusion The prevalence of multiple pregnancies was 1.99%, with 65.1% resulting in preterm births. Neonatal complications were notably more frequent in monochorionic twins. Monochorionic placenta and antepartum complications emerged as significant risk factors for preterm birth.

PurposeTo establish blastocyst freezing criteria for day 7 blastocyst (day 7 BL) for single vitrified-warmed blastocyst transfer (SVBT) by examining the diameter of blastocysts.MethodsPatients who underwent day 7 BL transfer cycles (1143 cycles, mean age: 38.5 ± 3.5) and randomly selected patients after 1:1 matching who underwent day 6 BL transfer cycles and day 2-single-embryo transfer (SET) cycles were used for analysis. Comparison of the miscarriage (per clinical pregnancy) and live birth rates were made among day 2-SET, day 7 BL, and day 6 BL. These blastocyst groups were stratified into six groups based on blastocyst diameter, namely, 180 μm, 190 μm, 200 μm, 210 μm, over 220 μm, and hatched, for making the freezing criteria.ResultsFor each diameter, 180 μm, 190 μm, 200 μm, 210 μm, over 220 μm, and hatched, the live birth rates of day 7 BL after SVBT were 9.0%, 11.9%, 11.5%, 15.6%, 20.0%, and 19.9%, respectively. Compared with the 14.6% live birth rate of the day 2-SET group, the live birth rate of 220 μm day 7 BL was significantly higher (P < 0.05) and was around the same in other diameter groups.ConclusionOur study demonstrates that sufficient live birth rates can be obtained after SVBT even from blastocysts on day 7 when blastocysts were vitrified at expanded blastocyst stage of over 180 μm of diameter or at hatched blastocyst stage and were transferred at the optimal time. This is the first study to establish a day 7 blastocyst freezing criteria using blastocyst diameter, which is an objective assessment way.

Objective To compare the perinatal outcome of singleton and twin pregnancies between natural and assisted conceptions. Design Systematic review of controlled studies published 1985-2002. Studies reviewed 25 studies were included of which 17 had matched and 8 had non-matched controls. Main outcome measures Very preterm birth, preterm birth, very low birth weight, low birth weight, small for gestational age, caesarean section, admission to neonatal intensive care unit, and perinatal mortality. Results For singletons, studies with matched controls indicated a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) for very preterm (< 32 weeks) and 2.04 (1.80 to 2.32) for preterm (< 37 weeks) birth in pregnancies after assisted conception. Relative risks were 3.00 (2.07 to 4.36) for very low birth weight (< 1500 g), 1.70 (1.50 to 1.92) for low birth weight (< 2500 g), 1.40 (1.15 to 1.71) for small for gestational age, 1.54 (1.44 to 1.66) for caesarean section, 1.27 (1.16 to 1.40) for admission to a neonatal intensive care unit, and 1.68 (1.11 to 2.55) for perinatal mortality. Results of the non-matched studies were similar. In matched studies of twin gestations, relative risks were 0.95 (0.78 to 1.15) for very preterm birth, 1.07 (1.02 to 1.13) for preterm birth, 0.89 (0.74 to 1.07) for very low birth weight, 1.03 (0.99 to 1.08) for low birth weight, 1.27 (0.97 to 1.65) for small for gestational age, 1.21 (1.11 to 1.32) for caesarean section, 1.05 (1.01 to 1.09) for admission to a neonatal intensive care unit, and 0.58 (0.44 to 0.77) for perinatal mortality. The non-matched studies mostly showed similar trends. Conclusions Singleton pregnancies from assisted reproduction have a significantly worse perinatal outcome than non-assisted singleton pregnancies, but this is less so for twin pregnancies. In twin pregnancies, perinatal mortality is about 40% lower after assisted compared with natural conception.

Maternal diet and nutritional status are of key importance with regard to the short- and long-term health outcomes of both the mother and the fetus. Multiple pregnancies are a special phenomenon in the context of nutrition. The presence of more than one fetus may lead to increased metabolic requirements and a faster depletion of maternal macro- and micro- nutrient reserves than in a singleton pregnancy. The aim of this systematic review was to gather available knowledge on the supply and needs of mothers with multiple pregnancies in terms of micronutrients and the epidemiology of deficiencies in that population. It was constructed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). The authors conducted a systematic literature search with the use of three databases: PubMed/MEDLINE, Scopus and Embase. The last search was run on the 18 October 2020 and identified 1379 articles. Finally, 12 articles and 1 series of publications met the inclusion criteria. Based on the retrieved studies, it may be concluded that women with multiple pregnancies might be at risk of vitamin D and iron deficiencies. With regard to other microelements, the evidence is either inconsistent, scarce or absent. Further in-depth prospective and population studies are necessary to determine if nutritional recommendations addressed to pregnant women require adjustments in cases of multiple gestations.

Introduction Multiple gestations impose greater physiological, psychological, and socioeconomic demands compared to singleton pregnancies. Given the limited data on the unique challenges and multifaceted needs of pregnant women with this condition, this study aimed to explore the lived experiences of these women regarding the challenges and needs associated with higher-order multiple pregnancies. Method This study employed a qualitative approach with a descriptive phenomenology design. Using a maximum variation purposive sampling method, we selected women from Western Iran who had experienced higher-order multiple pregnancies. Sampling continued until data saturation was reached. Data were collected through face-to-face, semi-structured, in-depth interviews, which had a mean duration of 73.44 ± 10.44 min. Data analysis was performed using Colaizzi’s seven-step method. The criteria of Lincoln and Guba were applied to ensure the trustworthiness and rigor of the findings. Results Participants’ experiences were encapsulated within five overarching themes and 20 sub-themes. These themes included: Crushed under the pressure and responsibilities, Multiplicity of life amidst profound loneliness, immersion in needs, Journey of Acceptance, and Living Amidst the Ethical Struggles. The mean age of participants was 32.5 ± 5.46 years. Furthermore, 75% of the pregnancies were triplets, and 75% were conceived through assisted reproductive techniques. Conclusion Women navigate these challenges through diverse adaptive and non-adaptive strategies, while articulating distinct needs whose fulfillment could ease complexities and foster acceptance of multiple pregnancy. Effectively addressing these multifaceted issues requires a comprehensive, multi-pronged approach by policymakers and healthcare leaders, encompassing supportive policies, specialized healthcare, prenatal education, essential facilities, and strengthened adaptive mechanisms.

Mild in-vitro fertilisation (IVF) treatment might lessen both patients' discomfort and multiple births, with their associated risks. We aimed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy resulting in term livebirth within 1 year compared with standard treatment, and can also reduce patients' discomfort, multiple pregnancies, and costs. We did a randomised, non-inferiority effectiveness trial. 404 patients were randomly assigned to undergo either mild treatment (mild ovarian stimulation with gonadotropin-releasing hormone [GnRH] antagonist co-treatment combined with single embryo transfer) or a standard treatment (stimulation with a GnRH agonist long-protocol and transfer of two embryos). Primary endpoints were proportion of cumulative pregnancies leading to term livebirth within 1 year after randomisation (with a non-inferiority threshold of −12·5%), total costs per couple up to 6 weeks after expected date of delivery, and overall discomfort for patients. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN35766970. The proportions of cumulative pregnancies that resulted in term livebirth after 1 year were 43·4% with mild treatment and 44·7% with standard treatment (absolute number of patients=86 for both groups). The lower limit of the one-sided 95% CI was −9·8%. The proportion of couples with multiple pregnancy outcomes was 0·5% with mild IVF treatment versus 13·1% (p<0·0001) with standard treatment, and mean total costs were €8333 and €10745, respectively (difference €2412, 95% CI 703–4131). There were no significant differences between the groups in the anxiety, depression, physical discomfort, or sleep quality of the mother. Over 1 year of treatment, cumulative rates of term livebirths and patients' discomfort are much the same for mild ovarian stimulation with single embryos transferred and for standard stimulation with two embryos transferred. However, a mild IVF treatment protocol can substantially reduce multiple pregnancy rates and overall costs.

Introduction The aim was to investigate the risk, prevalence, and clinical characteristics of cerebral palsy among children born after assisted reproductive technology (ART) in Norway. Material and methods All liveborn children from 2002 to 2015 were included. Information was collected from the Medical Birth Registry of Norway, linked to the Norwegian Quality and Surveillance Registry for Cerebral Palsy as of December 31, 2022. Logistic regression analyses were used to calculate the prevalence of cerebral palsy per 1000 live births after ART and natural conception with birth year as covariate, crude odds ratios (OR) for cerebral palsy among children born after ART using children born after natural conception as reference, and OR adjusted for potential confounders, with 95% confidence intervals (CI). Potential mediators of the association were studied in stratified analyses. Descriptive statistics were used to compare proportions in clinical characteristics among children with cerebral palsy born after ART and natural conception. Results Among 833 645 livebirths, 23 645 children were born after ART and of the latter 97 were diagnosed with cerebral palsy. The overall prevalence of cerebral palsy after ART was 4.10 per 1000 live births (95% CI 3.36–5.00), decreasing from 7.79 per 1000 in 2002 to 3.55 in 2015. Compared with children born after natural conception, the OR for cerebral palsy was 2.01 (95% CI 1.63–2.47) adjusted for mother's age at birth, parity, and pre‐pregnancy health. When restricted to singletons born at term, the adjusted OR for cerebral palsy was 1.13 (95% CI 0.76–1.69). The distribution of cerebral palsy subtypes and the severity of gross and fine motor function and associated impairments did not differ significantly between children with cerebral palsy born after ART and natural conception. Conclusions Children born after ART had a risk of cerebral palsy that was twice that of children born after natural conception. The increased risk of cerebral palsy after ART is likely attributed to multiple pregnancies and preterm births. The prevalence of cerebral palsy after ART decreased significantly during the study period, despite an increased use of ART in the population. The distribution of clinical characteristics did not differ between children with cerebral palsy born after ART and those born after a natural conception, suggesting that the risk factors for, and causes of cerebral palsy were similar. There is still an increased risk of cerebral palsy associated with assisted reproductive technology (ART), mainly attributable to multiple pregnancies and children born preterm. Despite an increase in children born after ART, the prevalence of cerebral palsy after ART has decreased. The distribution of clinical characteristics may suggest that risk factors for, and causes of cerebral palsy are similar in children born after ART and natural conception.