Guideline for the management of conception and pregnancy in thalassaemia syndromes: A British Society for Haematology Guideline.

This comprehensive guideline, developed by a representative group of UK-based medical experts specialising in haemoglobinopathies, addresses the management of conception and pregnancy in patients with thalassaemia. A systematic search of PubMed and EMBASE using specific keywords, formed the basis of the literature review. Key terms included "thalassaemia," "pregnancy," "Cooley's anaemia," "Mediterranean anaemia," and others, covering aspects such as fertility, iron burden and ultrasonography. The guideline underwent rigorous review by prominent organisations, including the Endocrine Society, the Royal College of Obstetricians and Gynaecologists (RCOG), the United Kingdom Thalassaemia Society and the British Society of Haematology (BSH) guideline writing group. Additional feedback was solicited from a sounding board of UK haematologists, ensuring a thorough and collaborative approach. The objective of the guideline is to equip healthcare professionals with precise recommendations for managing conception and pregnancy in patients with thalassaemia.

Effect of vitamin D on pregnancy in women with polycystic ovary syndrome: retrospective and prospective studies.

RESEARCH QUESTION: Does vitamin D affect the pregnancy rate of patients with polycystic ovary syndrome (PCOS) receiving ovulation-induction therapy? DESIGN: The retrospective study included 200 patients with PCOS and 200 healthy women. The prospective study included 160 patients with PCOS receiving vitamin D or placebo supplementation. Pregnancy rates were assessed after a maximum of three cycles of ovulation induction. Serum concentrations of 25-hydroxycalciferol [25-(OH)D3], LH, FSH, progesterone, oestradiol, testosterone and fasting insulin; LH/FSH ratio; and body mass index were evaluated. RESULTS: In the retrospective study, patients with PCOS had lower 25-(OH)D3 concentrations than healthy women, pregnant patients with PCOS had higher 25-(OH)D3 concentrations than non-pregnant patients with PCOS (both P = 0.000), and the pregnancy rate was lower in the vitamin-D-deficient group compared with the non-vitamin-D-deficient group (P = 0.022). In the prospective study, compared with placebo supplementation, vitamin D supplementation increased the serum concentration of 25-(OH)D3 (P = 0.000), and reduced the LH/FSH ratio, and concentrations of LH and testosterone significantly (all P ≤ 0.049). After the intervention, it was found that the LH/FSH ratio, and concentrations of LH and testosterone were significantly lower in both groups compared with pre-intervention (P = 0.000). After ovulation induction, the pregnancy rate was higher in patients in the vitamin D supplementation group compared with the placebo supplementation group (P = 0.049). CONCLUSIONS: Vitamin D deficiency is common in patients with PCOS, and vitamin-D-deficient patients with PCOS have lower pregnancy rates after ovulation induction compared with non-vitamin-D-deficient patients with PCOS. Vitamin D supplementation can improve the pregnancy rate and mitigate basic hormone disorders. Therefore, monitoring vitamin D supplementation and checking vitamin D concentrations before and during interventions are essential for patients with PCOS.

The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) is a therapeutic approach that is gaining attention for its potential in the treatment of poor ovarian response. This meta-analysis aimed to systematically review and analyze clinical studies to evaluate the impact of PRP on poor responders undergoing ovarian stimulation for IVF. METHODS: A comprehensive search was conducted in electronic databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify relevant studies published in English. The pooled data, such as pregnancy outcome, number of MII oocytes, number of transferable embryos, and ovarian reserve markers were analyzed using R version 4.2.3. RESULTS: A total of 10 trials were enrolled in the present meta-analysis. Following PRP treatment, live birth rate was found to be 16.6% (95% CI 8.8%-26.1%), while clinical pregnancy rate was observed to be 25.4% (95% CI 13.1%-39.9%). PRP pretreatment resulted in a higher number of MII oocytes (MD 1.073, 95% CI 0.720 to 1.427), a higher number of embryos (MD 0.946, 95% CI 0.569 to 1.323), a higher antral follicle count (MD 1.117; 95% CI 0.689 to 1.544), and the change of hormone levels. CONCLUSIONS: Among the studies evaluated in this review, PRP showed promising results in poor responder. Further research is required to clarify the potential role of PRP in female reproductive health.

What is the context? The incidence of poor ovarian response following ovarian stimulation ranges globally from 5.6% to 35.1%.Although various interventions have been implemented in patients with POR, there is a lack of empirical evidence demonstrating the superiority of any of these therapies over one another.Platelet-rich plasma, which is rich in growth factors that have been implicated in cellular growth, differentiation, angiogenesis, and tissue repair, is emerging as a promising therapeutic modality.Limited data determines the viability of PRP as an alternative therapy for POR patients, but further evidence is needed to quantify this effect.What is new? To the best of our knowledge, this is the first systematic review and meta-analysis that investigated the efficacy of PRP on women with POR, including ten trials and 876 patients.This review provides a comprehensive overview of the existing evidence on the utilization of PRP in poor responders, while also emphasizing the primary limitations in the literature and the necessity for future research based on evidence.What is the impact? Among the studies evaluated in this review, PRP showed a potential positive impact on the regulation of sex hormone levels, ovarian response, and pregnancy outcomes.

Assessing the impact of medically assisted reproduction on autism spectrum disorder risk.

PURPOSE: Techniques of medically assisted reproduction interact with the embryo at crucial developmental stages, yet their impact on the fetus and subsequent child's health remains unclear. Given rising infertility rates and more frequent use of fertility treatments, we aimed to investigate if these methods heighten the risk of autism spectrum disorder (ASD) in children. METHODS: A population-based cohort study was conducted at Soroka University Medical Center, a tertiary referral hospital, encompassing singleton births. The incidence of ASD in offspring, incorporating either hospital or community-based diagnoses, was compared in relation to the conception method. To examine the cumulative incidence of ASD, a Kaplan-Meier survival curve was utilized. Cox proportional hazards model was employed to adjust for confounders. RESULTS: Among 115,081 pregnancies, 0.5% involved ovulation induction (OI) and 1.7% in vitro fertilization (IVF), with the rest conceived naturally. Fertility treatments were more common in older patients and linked to more diabetes, hypertensive disorders, preterm, and cesarean deliveries. Out of 767 ASD diagnoses, offspring from OI and IVF had higher initial ASD rates (2.1% and 1.3%) than natural conceptions (0.6%). In a Cox model accounting for maternal age, ethnicity, and gender, neither OI nor IVF was significantly associated with ASD. The adjusted hazard ratios were 0.83 (95% CI 0.48-1.43) for OI and 1.34 (95% CI 0.91-1.99) for IVF. When considering fertility treatments combined, the association with ASD remained non-significant (aHR 1.11, 95% CI 0.80-1.54, p = 0.52). CONCLUSION: Fertility treatments, including OI and IVF, do not exhibit a significant association with heightened ASD risk in offspring.

Ovulation induction and subfertile untreated conception groups offer improved options for interpreting risks associated with ART.

PURPOSE: To identify and characterise appropriate comparison groups for population studies of health outcomes in ART-conceived births: ovulation induction (OI), subfertile untreated and fertile natural conceptions. Our secondary objective was to examine whether known risks of pregnancy complications and adverse birth outcomes in ART births are elevated in comparison with subfertile (untreated and OI) conception groups. METHODS: We linked State and Commonwealth datasets to identify all live and stillbirths (≥ 20 weeks) in Western Australia from 2003 to 2014 by method of conception. Demographic characteristics, maternal pre-existing conditions, adverse obstetric history and pregnancy complications were compared across conception groups. Generalised estimating equations were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CI) for pregnancy complications and birth outcomes in singletons. RESULTS: We identified 9456 ART, 3870 OI, 11,484 subfertile untreated and 303,921 fertile naturally conceived deliveries. OI and subfertile untreated groups more closely resembled the ART group than the fertile group; however, some differences remained across parity, maternal age, pre-existing conditions and obstetric history. In multivariate analyses, ART singletons had greater risks of placental problems (e.g. placenta praevia aRR 2.42 (95% CI 1.82-3.20)) and adverse birth outcomes (e.g. preterm birth aRR 1.38 (95% CI 1.25-1.52)) than the subfertile untreated group, while OI singletons were more similar to the subfertile group with higher risk of preeclampsia and gestational diabetes. CONCLUSION: OI and subfertile untreated conception groups offer improved options for interpreting health outcomes in ART births. Pregnancy complications (particularly placental disorders) and adverse outcomes at delivery are more common following ART.

Kisspeptin expression during menstruation in PCOS patients undergoing ovulation induction and the correlation with early pregnancy.

PURPOSE: To examine the pattern of kisspeptin expression throughout the menstrual cycle in polycystic ovary syndrome (PCOS) patients under the ovulation induction and identify any possible associations with early pregnancy. MATERIALS AND METHODS: A prospective cohort of 80 PCOS women who expressed the desire for fertility was enrolled in this study. All of them received the ovulation induction by using letrozole. Levels of kisspeptin, luteinizing hormone (LH), and estradiol (E2) were measured at three different time points during menstruation. The early pregnancy rate was recorded for the study participants after three ovulation cycles. RESULTS: Kisspeptin levels varied regularly during the menstrual cycle, reaching a peak on the day of hCG injection and decreasing after ovulation. There was no significant correlation between kisspeptin and LH levels. Basal kisspeptin levels decreased after letrozole treatment without a significant difference while LH and E2 levels decreased significantly. PCOS participants who became pregnant early had higher basal kisspeptin levels compared to non-pregnant PCOS patients, which had a significant difference (P = 0.006). And the average basal kisspeptin level in pregnant patients was 2293.0 ± 398.7 pg/ml, with a 95% confidence interval of 1511.5-3074.5 pg/ml. CONCLUSION: Kisspeptin levels in PCOS women undergoing ovulation induction showed a regular variation, which was similar with the healthy women reported in previous studies. The use of LE may result in PCOS endocrine improvement and fertility achievement. In a certain range, kisspeptin might be a potential predictor for early pregnancy in PCOS patients as people with slightly higher basal kisspeptin levels seemed more likely to be pregnant.

Long-term outcomes of switching to gonadotrophins versus continuing with clomiphene citrate, with or without intrauterine insemination, in women with normogonadotropic anovulation and clomiphene failure: follow-up study of a factorial randomized clinical trial.

STUDY QUESTION: What are the long-term outcomes after allocation to use of gonadotrophins versus clomiphene citrate (CC) with or without IUI in women with normogonadotropic anovulation and clomiphene failure? SUMMARY ANSWER: About four in five women with normogonadotropic anovulation and CC failure had a live birth, with no evidence of a difference in pregnancy outcomes between the allocated groups. WHAT IS KNOWN ALREADY: CC has long been used as first line treatment for ovulation induction in women with normogonadotropic anovulation. Between 2009 and 2015, a two-by-two factorial multicentre randomized clinical trial in 666 women with normogonadotropic anovulation and six cycles of CC failure was performed (M-ovin trial). This study compared a switch to gonadotrophins with continued treatment with CC for another six cycles, with or without IUI within 8 months. Switching to gonadotrophins increased the chance of conception leading to live birth by 11% over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth. The addition of IUI did not significantly increase live birth rates. STUDY DESIGN, SIZE, DURATION: In order to investigate the long-term outcomes of switching to gonadotrophins versus continuing treatment with CC, and undergoing IUI versus continuing with intercourse, we conducted a follow-up study. The study population comprised all women who participated in the M-ovin trial. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participating women were asked to complete a web-based questionnaire. The primary outcome of this study was cumulative live birth. Secondary outcomes included clinical pregnancies, multiple pregnancies, miscarriage, stillbirth, ectopic pregnancy, fertility treatments, neonatal outcomes and pregnancy complications. MAIN RESULTS AND THE ROLE OF CHANCE: We approached 564 women (85%), of whom 374 (66%) responded (184 allocated to gonadotrophins; 190 to CC). After a median follow-up time of 8 years, 154 women in the gonadotrophin group had a live birth (83.7%) versus 150 women in the CC group (78.9%) (relative risk (RR) 1.06, 95% CI 0.96-1.17). A second live birth occurred in 85 of 184 women (49.0%) in the gonadotrophin group and in 85 of 190 women (44.7%) in the CC group (RR 1.03, 95% CI 0.83-1.29). Women allocated to gonadotrophins had a third live birth in 6 of 184 women (3.3%) and women allocated to CC had a third live birth in 14 of 190 women (7.4%). There were respectively 12 and 11 twins in the gonadotrophin and CC groups. The use of fertility treatments in the follow-up period was comparable between both groups. In the IUI group, a first live birth occurred in 158 of 192 women (82.3%) and while in the intercourse group, 146 of 182 women (80.2%) reached at least one live birth (RR: 1.03 95% CI 0.93-1.13; 2.13%, 95% CI -5.95, 10.21). LIMITATIONS, REASONS FOR CAUTION: We have complete follow-up results for 57% of the women.There were 185 women who did not respond to the questionnaire, while 102 women had not been approached due to missing contact details. Five women had not started the original trial. WIDER IMPLICATIONS OF THE FINDINGS: Women with normogonadotropic anovulation and CC failure have a high chance of reaching at least one live birth. In terms of pregnancy rates, the long-term differences between initially switching to gonadotrophins are small compared to continuing treatment with CC. STUDY FUNDING/COMPETING INTEREST(S): The original study received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). A.H. reports consultancy for development and implementation of a lifestyle App, MyFertiCoach, developed by Ferring Pharmaceutical Company. M.G. receives unrestricted grants for scientific research and education from Ferring, Merck and Guerbet. B.W.M. is supported by an NHMRC Investigatorgrant (GNT1176437). B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: This follow-up study was registered in the OSF Register, https://osf.io/pf24m. The original M-ovin trial was registered in the Netherlands Trial Register, number NTR1449.

Recent clomiphene citrate exposure does not impact subsequent clinical outcomes in single euploid frozen embryo transfer cycles.

STUDY QUESTION: Do infertile couples who recently utilized clomiphene citrate (CC) for ovulation induction or ovarian stimulation (<90 days previously) followed by a single euploid embryo transfer (SEET) have lower implantation potential compared with patients who were not exposed to CC within 90 days before embryo transfer (ET)? SUMMARY ANSWER: There does not appear to be an association between recent CC exposure and lower implantation potential in patients who undergo a frozen embryo transfer (FET) of euploid embryos. WHAT IS KNOWN ALREADY: Clomiphene has been found to be associated with lower pregnancy rates when compared against other ovarian stimulation medications. The majority of published research about the effects of CC on implantation potential suggest an anti-estrogenic effect on the endometrium. Quality evidence and information about utilization of CC and its effect on implantation potential after euploid ETs is lacking in the literature. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study with propensity score matching was carried out. We included all patients that underwent an autologous SEET from September 2016 to September 2022 at a single academic-private ART center. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study group included patients that had utilized CC during either ovulation induction cycles and/or controlled ovarian stimulation at least 90 days before FET. A propensity score-matched control group of patients that were unexposed to CC within 90 days prior to SEET was used for comparisons. The primary outcome was positive pregnancy test (defined as a positive serum ß-hCG measured 9 days after ET), with other outcomes including clinical pregnancy, ongoing pregnancy, biochemical pregnancy loss, and clinical pregnancy loss rates per SEET. Multivariate regression analyses fitted with generalized estimating equations were utilized to analyze if there was an association between CC utilization and IVF outcomes. Furthermore, the study evaluated the cumulative effect of CC and endometrial receptivity in vivo and subsequent IVF outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 593 patients with utilization of CC in <90 days before ET were compared with 1779 matched controls. Positive pregnancy test rates were comparable among the control group and the CC exposed groups, respectively (74.3% versus 75.7%, P = 0.79), as were clinical pregnancy (64.0% versus 65.0%, P = 0.60), ongoing pregnancy (51.8% versus 53.2%, P = 0.74), biochemical pregnancy loss (15.7% versus 14.03%, P = 0.45), and clinical pregnancy loss rates were also comparable among cohorts (17.1% versus 18.1%, P = 0.71). No association was found between utilization of clomiphene and lower implantation rates (adjusted odds ratio 0.95, 95% CI 0.76-1.18). Also, no differences were observed in sub-analyses based on multiple CC utilization periods. Finally, no association was found between the number of consecutive cumulative clomiphene cycles and sub-optimal IVF outcomes. LIMITATIONS, REASONS FOR CAUTION: The study has inherent bias that originated from its retrospective design. Serum levels of CC were not measured and sample size for the sub-analyses was small. WIDER IMPLICATIONS OF THE FINDINGS: There does not appear to be an association between recent CC exposure and lower implantation potential in patients who undergo a FET of euploid embryos. This finding remains consistent, even in patients who undergo multiple, consecutive clomiphene cycles prior to ET. There were no long-term effects of CC on endometrial development and clinical characteristics examined in this study. Patients that utilized CC medication prior to a SEET cycle for either ovarian stimulation or ovulation induction, can be assured that there is no evidence of a residual effect of recent CC administration that could jeopardize their pregnancy probability. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for the realization of this study. A.C. is advisor and/or board member of Sema4 (stakeholder in data) and Progyny. The other authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Predicting pregnancy chances leading to term live birth in oligo/anovulatory women diagnosed with PCOS.

RESEARCH QUESTION: Which patient features predict the time to pregnancy (TTP) leading to term live birth in infertile women diagnosed with polycystic ovary syndrome (PCOS)? DESIGN: Prospective cohort follow-up study was completed, in which initial standardized phenotyping was conducted at two Dutch university medical centres from January 2004 to January 2014. Data were linked to the Netherlands Perinatal Registry to obtain pregnancy outcomes for each participant. All women underwent treatment according to a standardized protocol, starting with ovulation induction as first-line treatment. Predictors of pregnancies (leading to term live births) during the first year after PCOS diagnosis were evaluated. RESULTS: A total of 1779 consecutive women diagnosed with PCOS between January 2004 and January 2014 were included. In the first year following screening, 659 (37%) women with PCOS attained a pregnancy leading to term birth (≥37 weeks of gestational age). A higher chance of pregnancy was associated with race, smoking, body mass index (BMI), insulin, total testosterone and sex hormone-binding globulin (SHBG) concentrations (c-statistic = 0.59). CONCLUSIONS: Predictors of an increased chance of a live birth include White race, no current smoking, lower BMI, insulin and total testosterone concentrations, and higher SHBG concentrations. This study presents a nomogram to predict the chances of achieving a pregnancy (leading to a term live birth) within 1 year of treatment.

Ovulation induction using sequential letrozole/gonadotrophin in infertile women with PCOS: a randomized controlled trial.

RESEARCH QUESTION: Is sequential letrozole/human menopausal gonadotrophin (HMG) superior to letrozole alone in ovulation induction and pregnancy promotion among infertile women with polycystic ovary syndrome (PCOS)? DESIGN: This open-label randomized controlled trial comparing sequential letrozole/HMG and letrozole alone included 174 participants enrolled from August 2019 to January 2020 at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. Infertile women aged between 18 and 40 years who met Rotterdam criteria for PCOS and without other known causes of infertility were selected for this study. Patients were randomly assigned at a 1:1 ratio to receive 2.5 mg letrozole on cycle days 3-7 (n = 87) or 2.5 mg letrozole on cycle days 3-7 with a sequential injection of 75 IU HMG on cycle days 8-10 for one treatment cycle (n = 87). The pregnancy outcome was recorded after one treatment cycle. RESULTS: Women receiving sequential treatment achieved a significantly higher ovulation rate than those in the letrozole group (90.8% versus 70.1%, P = 0.001) and the live birth rate of the sequential group was significantly higher than that of the letrozole protocol (23.0% versus 10.3%, P = 0.025); there was no statistical variation with respect to adverse events. CONCLUSIONS: The data suggest that the sequential letrozole/HMG protocol may be superior to the letrozole alone protocol in terms of ovulation induction and pregnancy promotion among infertile women with PCOS.

In praise of ovulation induction for the management of anovulatory subfertility.

Rapid advances in assisted reproductive technology have revolutionized fertility treatments for couples worldwide seeking a pregnancy. Although this is promising, concerns are emerging over the overuse of unnecessary assisted conception treatments, particularly among couples with anovulatory subfertility. Some experts are calling for the cessation of ovulation induction as the primary treatment of anovulatory subfertility in favour of more sophisticated assisted conception treatments. In the absence of other causes of subfertility, ovulation induction in patients with type 1 and type 2 anovulation disorders can achieve an up to 80% ovulation rate with a 40% cumulative pregnancy rate and few adverse effects. Considering the various risks and high costs associated with assisted reproductive technology treatments, it is hard to argue for their cost-effectiveness when simpler, safer and cheaper pharmacological ovulation induction could achieve comparable pregnancy rates. We argue here for the safe, effective and ethical use of ovulation induction in this population, supplemented by a judicious use of assisted conception treatments. We emphasize the essential role of ovulation induction as a first-line intervention for couples with anovulatory subfertility delivered within a patient-centred multidisciplinary care model and with a clear escalation pathway to use assisted reproductive technology treatments based on the person's response, characteristics and treatment preference.

Ovulation induction in anovulatory infertility is obsolete.

Women with polycystic ovary syndrome make up the vast majority of patients with anovulatory infertility. The commonly accepted treatment guidelines recommend ovulation induction for timed intercourse as the first-line treatment. After a 2-year treatment period, the cumulative pregnancy rates with a singleton live-born baby reached 71% and 78% in two prospective studies. Despite aiming for monofollicular growth, multifollicular responses with subsequent multiple/higher order multiple pregnancies are a dreaded risk associated with ovarian induction. However, the lengthy treatment, the increase of maternal age and the psychological effects of 'obligatory intercourse' are also factors challenging the concept of ovarian induction as the first treatment approach in anovulatory infertility. Nowadays, individualized IVF treatment with cycle segmentation, freeze-all strategies and single-embryo transfers in frozen embryo transfer cycles dramatically reduces the risk of multiple pregnancies, and a cumulative pregnancy rate of 83% can be achieved over three complete cycles, thereby reducing exposure to fertility medication and time to pregnancy. Although on first sight ovarian induction might present the easier and less costly approach, efficient and individualized IVF treatments with low complication rates and the chance of preventing multiple pregnancies challenge this concept, and it seems that the time has come to abandon ovarian induction in anovulatory infertility.

Perinatal and pediatric outcomes associated with the use of fertility treatment: a population-based retrospective cohort study in Ontario, Canada.

BACKGROUND: Around 2% of births in Ontario, Canada involve the use of assisted reproductive technology (ART), and it is rising due to the implementation of a publicly funded ART program in 2016. To better understand the impact of fertility treatments, we assessed perinatal and pediatric health outcomes associated with ART, hormonal treatments, and artificial insemination compared with spontaneously conceived births. METHODS: This population-based retrospective cohort study was conducted using provincial birth registry data linked with fertility registry and health administrative databases in Ontario, Canada. Live births and stillbirths from January 2013 to July 2016 were included and followed to age one. The risks of adverse pregnancy, birth and infant health outcomes were assessed by conception method (spontaneous conception, ART - in vitro fertilization and non-ART - ovulation induction, intra-uterine or vaginal insemination) using risk ratios and incidence rate ratios with 95% confidence intervals (CI). Propensity score weighting using a generalized boosted model was applied to adjust for confounding. RESULT(S): Of 177,901 births with a median gestation age of 39 weeks (IQR 38.0-40.0), 3,457 (1.9%) were conceived via ART, and 3,511 (2.0%) via non-ART treatments. There were increased risks (adjusted risk ratio [95% CI]) of cesarean delivery (ART: 1.44 [1.42-1.47]; non-ART: 1.09 [1.07-1.11]), preterm birth (ART: 2.06 [1.98-2.14]; non-ART: 1.85 [1.79-1.91]), very preterm birth (ART: 2.99 [2.75-3.25]; non-ART: 1.89 [1.67-2.13]), 5-min Apgar < 7 (ART: 1.28 [1.16-1.42]; non-ART: 1.62 [1.45-1.81]), and composite neonatal adverse outcome indicator (ART: 1.61 [1.55-1.68]; non-ART: 1.29 [1.25-1.34]). Infants born after fertility treatments had increased risk of admission to neonatal intensive care unit (ART: 1.98 [1.84-2.13]; non-ART: 1.59 [1.51-1.67]) and prolonged birth admission (≥ 3 days) (ART: 1.60 [1.54-1.65]; non-ART: 1.42 [1.39-1.45]). The rate of emergency and in-hospital health services use within the first year was significantly increased for both exposure groups and remained elevated when limiting analyses to term singletons. CONCLUSION(S): Fertility treatments were associated with increased risks of adverse outcomes; however, the overall magnitude of risks was lower for infants conceived via non-ART treatments.

Clomiphene citrate plus letrozole versus clomiphene citrate alone for ovulation induction in infertile women with ovulatory dysfunction: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction. METHODS: A randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A "combination group" received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a "CC-alone group" received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events. RESULTS: One hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group. CONCLUSIONS: Our study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study. TRIAL REGISTRATION: The study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.

The Value of Anti-Müllerian Hormone in Predicting Ovulation Induced by Aromatase Inhibitors in Women With Polycystic Ovary Syndrome.

OBJECTIVES: This study aimed to evaluate the value of anti-Müllerian hormone (AMH) in predicting ovulation induced by aromatase inhibitors (AI) and pregnancy outcomes in women with polycystic ovary syndrome (PCOS). METHODS: From January 2018 to December 2020, this prospective cohort study enrolled women with PCOS aged between 18 and 45 years who underwent ovulation induction using AI protocol and intrauterine insemination (IUI) for infertility at a Center for Reproductive Endocrinology and Infertility, University Hospital. Receiver operating characteristic curves were used to estimate the chance of ovulation responses and pregnancy outcomes. RESULTS: In total, 64% of 65 women with PCOS were recruited following AI treatment, and the clinical pregnancy rate was 19.4% following IUI. Patients who experienced ovulation had a lower mean serum AMH concentration than non-responders (7.11 ng/mL vs. 8.95 ng/mL, respectively), but the difference was not statistically significant. Between the pregnancy and non-pregnancy groups, statistically significant differences in AMH concentrations were observed (8.71 ng/mL vs. 6.73 ng/mL, respectively, P = 0.040). The area under the curve of the receiver operating characteristic for non-ovulation prediction was 0.445, 95% CI (0.284-0.606) with P = 0.467, and for clinical pregnancy was 0.735, 95% CI (0.561-0.910) with P = 0.104. CONCLUSIONS: In women with PCOS, the AMH level does not predict ovarian responsiveness to AI treatment, but it does predict the success of IUI cycles.

Ovulation induction with letrozole and dexamethasone in infertile patients with letrozole-resistant polycystic ovary syndrome.

PURPOSE: To assess efficacy of adjuvant dexamethasone during letrozole cycles for ovulation induction (OI) in women with letrozole-resistant polycystic ovary syndrome (PCOS). METHODS: We retrospectively evaluated 42 cycles of OI from 28 infertile women with letrozole-resistant PCOS between September 2019 and November 2022. Letrozole was initiated on cycle day 3 for 5 days and increased via a stair-step approach to 7.5 mg as indicated. Patients were deemed letrozole-resistant if no dominant follicle was identified on transvaginal ultrasound following this dose. Resistant patients then received 5 additional days of letrozole 7.5 mg with low-dose dexamethasone 0.5 mg for 7 days and had a repeat ultrasound. The primary outcome was ovulation rate determined by the presence of a dominant follicle on ultrasound. Secondary outcomes included endometrial thickness, number of measurable follicles, and pregnancy outcomes among responders. RESULTS: Twenty-two of 28 (79%) letrozole-resistant PCOS patients had evidence of ovulation after the addition of dexamethasone in 35 out of 42 (83%) cycles. Clinical pregnancy occurred in 20% of ovulatory cycles with a cumulative rate of 32%. All clinical pregnancies resulted in a live birth. Patients who responded to adjuvant dexamethasone were more likely to have a shorter duration of infertility; however, there were no differences in other demographics, serum androgens including DHEA-S, or pretreatment glycemic status. CONCLUSION: Adding dexamethasone to letrozole increased ovulation rates in letrozole-resistant PCOS patients undergoing OI with similar pregnancy outcomes to prior studies. The addition of dexamethasone is an effective, inexpensive, and safe option for PCOS patients otherwise at risk for cycle cancelation.

Intrauterine hydatidiform mole complicated with tubal ectopic pregnancy: a case report.

Heterotopic pregnancies are rare pathological pregnancy disorders in clinical practice. However, the number of cases has increased with the widespread use of ovulation induction drugs in recent years. The clinical manifestations of heterotrophic pregnancies are diverse and easy to missed or misdiagnosed. A 33-year-old married Gravida1 Para 0 + 0 patient was admitted on December 8, 2020 with intermittent abdominal pain 18 days after uterine curettage for complete hydatidiform mole of 8 weeks gestation. She had ovulation-promoting drugs prior to the index pregnancy. Hysteroscopic-directed endometrial biopsy and laparoscopic left tubal surgery were offered to her; and she is being followed up with serial pelvic ultrasounds and ß-Human Chorionic Gonadotrophin (ßHCG) assays. This case study presents a case of intrauterine hydatidiform mole complicated with tubal pregnancy to highlight the problems associated with its diagnosis and treatment.

Comparative Study Of Combined Co-Enzyme Q10 And Clomiphene Citrate Vs Clomiphene Citrate Alone For Ovulation Induction In Patients With Polycystic Ovarian Syndrome.

A total of 136 patients with PCOS were followed through the Department of the Obstetrics and Gynaecology, Unit-IV, Lady Aitchison Hospital, Lahore. Patients were randomly divided by lottery method into two groups i.e., Group-A (CoQ10 plus Clomiphene citrate) and Group-B (Clomiphene citrate alone). The selected patients in the study group (group-A) were given Clomiphene citrate 100mg/day from cycle days 2-6 for 45 days (2 cycles) and CoQ10 in a dose of 50mg soft gel capsules thrice per day starting at cycle day-2, until HCG administration. Patients in controlled group (group 21 B) received Clomiphene citrate 100mg/day twice a day cycle for 45 days. Data were analysed in SPSS v25.0. In group-A (CoQ10 plus Clomiphene citrate), successful ovulation induction was noted in 16 (23.5%) patients, showing that with the addition of CoQ10, the chances of ovulation induction increased.

Chlormadinone acetate in progestin-primed ovarian stimulation does not negatively affect clinical results.

Purpose: To investigate whether progestin-primed ovarian stimulation (PPOS) with chlormadinone acetate (CMA) adversely affects clinical results and neonatal outcomes, or causes congenital deformities. Methods: This retrospective study was conducted at private IVF clinic from November 2018 to November 2021. Women underwent oocyte retrieval using gonadotropin-releasing hormone (GnRH) antagonist protocol (n = 835) or PPOS protocol (n = 57) were included. Eligible patients were normal ovarian responders (aged <40, AMH ≧1.0 ng/mL) with freeze-all cycle. Embryo developments, clinical results, or neonatal outcomes of singletons derived from transfer of frozen single blastocysts were compared within each group. Results: Patient characteristics were similar in both groups. The median LH level (mIU/mL) at trigger in the GnRH antagonist group [2.0 (1.2-3.7)] was significantly higher than in the PPOS group [0.9 (0.3-1.7)]. There was no cycle with premature LH surge in the PPOS group. Fertilization and blastocyst formation rates did not differ significantly between groups. Furthermore, clinical outcomes were also similar in the two groups. Congenital abnormality rates did not differ significantly [0.9% (3/329), 0.0% (0/17)]. Conclusions: CMA using ovarian stimulation did not negatively affect clinical results. Our data suggest that PPOS with CMA is an appropriate ovarian stimulation method for normal ovarian responders.

Effects of controlled ovarian stimulation on thyroid function during pregnancy†.

Controlled ovarian stimulation (COS) is a major component of assisted reproductive technologies. Clinically, it has been observed that some women experience changes in thyrotropin levels following COS, which then bring about subclinical hypothyroidism and may adversely affect conception. Studies have also shown that the specific degree as well as the tendency of changes in thyroid function vary with differences in thyroid function before pregnancy, thyroid autoimmunity, the COS regimen, and the observation time point. However, the associated pathophysiological mechanism of the effects of COS on pregnancy has not yet been fully elucidated. This may be because increased estradiol levels, caused by COS, induce increased levels of thyroxine-binding globulin, resulting in a decrease in free thyroxine (FT4) level and an increase in TSH level. Conversely, it has also been observed that human chorionic gonadotropin (hCG) can act directly on thyroid cells, exerting opposite effects on FT4 and TSH levels. Additionally, the effects of COS on thyroid function may be more pronounced, especially in women with autoimmune thyroid disease or thyroid dysfunction before pregnancy, ultimately leading to subclinical hypothyroidism. Here, we review recent research progress regarding the effects of COS on thyroid function during pregnancy.