The reproductive potential of vitrified-warmed euploid embryos declines following repeated uterine transfers.

BACKGROUND: Recurrent implantation failure (RIF) represents a vague clinical condition with an unclear diagnostic challenge that lacks solid scientific underpinning. Although euploid embryos have demonstrated consistent implantation capabilities across various age groups, a unanimous agreement regarding the advantages of preimplantation genetic testing for aneuploidy (PGT-A) in managing RIF is absent. The ongoing discussion about whether chromosomal aneuploidy in embryos significantly contributes to recurrent implantation failure remains unsettled. Despite active discussions in recent times, a universally accepted characterization of recurrent implantation failure remains elusive. We aimed in this study to measure the reproductive performance of vitrified-warmed euploid embryos transferred to the uterus in successive cycles. METHODS: This observational cohort study included women (n = 387) with an anatomically normal uterus who underwent oocyte retrieval for PGT-A treatment with at least one biopsied blastocyst, between January 2017 and December 2021 at a university-affiliated public fertility center. The procedures involved in this study included ICSI, blastocyst culture, trophectoderm biopsy and comprehensive 24-chromosome analysis of preimplantation embryos using Next Generation Sequencing (NGS). Women, who failed a vitrified-warmed euploid embryo transfer, had successive blastocyst transfer cycles (FET) for a total of three using remaining cryopreserved euploid blastocysts from the same oocyte retrieval cycle. The primary endpoints were sustained implantation rate (SIR) and live birth rate (LBR) per vitrified-warmed single euploid embryo. The secondary endpoints were mean euploidy rate (m-ER) per cohort of biopsied blastocysts from each patient, as well as pregnancy and miscarriage rates. RESULTS: The mean age of the patient population was 33.4 years (95% CI 32.8-33.9). A total of 1,641 embryos derived from the first oocyte retrieval cycle were biopsied and screened. We found no associations between the m-ER and the number of previous failed IVF cycles among different ranges of maternal age at oocyte retrieval (P = 0.45). Pairwise comparisons showed a significant decrease in the sustained implantation rate (44.7% vs. 30%; P = 0.01) and the livebirth rate per single euploid blastocyst (37.1% vs. 25%; P = 0.02) between the 1st and 3rd FET. The cumulative SIR and LBR after up to three successive single embryo transfers were 77.1% and 68.8%, respectively. We found that the live birth rate of the first vitrified-warmed euploid blastocyst transferred decreased significantly with the increasing number of previously failed IVF attempts by categories (45.3% vs. 35.8% vs. 27.6%; P = 0.04). A comparable decrease in sustained implantation rate was also observed but did not reach statistical significance (50% vs. 44.2 vs. 37.9%; P = NS). Using a logistic regression model, we confirmed the presence of a negative association between the number of previous IVF failed attempts and the live birth rate per embryo transfer cycle (OR = 0.76; 95% CI 0.62-0.94; P = 0.01). CONCLUSIONS: These findings are vital for enhancing patient counseling and refining management strategies for individuals facing recurrent implantation failure. By tailoring interventions based on age and ovarian reserve, healthcare professionals can offer more personalized guidance, potentially improving the overall success rates and patient experiences in fertility treatments. TRIAL REGISTRATION NUMBER: N/A.

The Effects of Long-Term Dienogest Therapy on In Vitro Fertilization Outcomes in Women with Endometriosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Assessing dienogest's efficacy in endometriosis patients undergoing in vitro fertilization (IVF). DATA SOURCES: Systematic search in databases (PubMed, MEDLINE, Embase, Web of Science, Cochrane CENTRAL, Google Scholar) until 1 October 2022. STUDY SELECTIONS: Randomized trials and observational studies comparing extended dienogest pre-treatment, no pre-treatment, or gonadotropin-releasing hormone (GnRH) agonist pre-treatment in endometriosis-linked IVF. OUTCOME MEASURES: live birth, clinical pregnancy rates, oocytes collected, miscarriage rate, gonadotropin consumption. DATA EXTRACTIONS AND SYNTHESES: Two authors independently assessed eligibility. Dichotomous variables were analyzed via a random-effect model and Mantel-Haenszel method to calculate weighted estimates and 95% confidence intervals (CI). I2 statistic gauged study heterogeneity; GRADE criteria evaluated evidence quality. CONCLUSIONS: Out of 191 publications, five studies with 723 participants were included. Uncertainty persists on whether prolonged dienogest affects live birth (RR 1.42, 95% CI 0.29 to 6.84; 3 studies, n = 289; I2 86%) and clinical pregnancy rates (RR 1.33, 95% CI 0.31 to 5.65; 3 studies, n = 289; I2 86%) compared to conventional IVF. Moreover, uncertainty remains regarding intervention impact on live birth (RR 1.46, 95% CI 0.63 to 3.37; 1 study, n = 34) and clinical pregnancy rates (RR 1.32, 95% CI 0.78 to 2.23; 3 studies, n = 288; I2 0%) versus long-term GnRH agonist therapy before IVF. Given limited data and very low evidence quality, doubts arise about the benefits of long-term dienogest pre-treatment before conventional IVF in endometriosis patients.

Split daily recombinant human LH dose in hypogonadotrophic hypogonadism: a nonrandomized controlled pilot study.

This prospective controlled nonrandomized pilot study was conducted to investigate whether split daily doses of recombinant human LH (rHLH) is more efficacious than the single daily dose in supporting follicular development and ovulation in primary hypogonadotrophic hypogonadism (HH). Twenty-seven women with HH received a 150 IU fixed daily subcutaneous dose of recombinant human FSH, supplemented by 75 IU daily dose of rHLH given either as a single dose (n=9; single-dose group) or four equally divided doses (n=18; split-dose group). Ovulation was defined by three efficacy end points: at least one follicle ⩾17mm in diameter, pre-ovulatory serum oestradiol ⩾400pmol/l and a midluteal progesterone ⩾25nmol/l. Although lacking statistical significance, the proportion of women in the rHLH split-dose group who fulfilled all three end points was higher than the single-dose group (72.2% versus 55.6%). Women in the split-dose group achieved higher serum oestradiol concentrations per follicle, endometrial thickness measurements and numbers of follicles than in the single-dose group (not statistically significant). The odds ratio for ovulation rate was 2.08 (not statistically significant). There were no serious untoward side effects. Administering rHLH in split daily doses could provide superior results compared with the traditional single daily dose. We conducted this clinical study to investigate whether a split daily dose protocol of recombinant human LH (rHLH) is more efficacious than the single daily dose in supporting follicular development and ovulation in primary hypogonadotrophic hypogonadism (HH). HH is an uncommon entity that can lead to very low or undetectable serum gonadotrophin concentrations. It manifests in anovulation, amenorrhoea and subsequent infertility. Twenty-seven women with HH received a 150 IU fixed daily subcutaneous dose of recombinant human FSH, supplemented by a 75 IU daily dose of rHLH given either as a single dose (n=9; single-dose group) or four equally divided doses (n=18; split-dose group). Ovulation was defined by these three efficacy end points: at least one follicle ⩾17mm in mean diameter, pre-ovulatory serum oestradiol concentration ⩾400pmol/l and a midluteal progesterone concentration ⩾25nmol/l. The proportion of women in the rHLH split-dose group who fulfilled all three end points was higher than the single-dose group (72.2% versus 55.6%). Women in the split-dose group achieved higher serum oestradiol concentrations per follicle, endometrial thickness measurements and numbers of follicles than in the single-dose group, without statistical significance. Women who received the split-dose regimen were more likely to have ovulation than the other group. We had no serious problematic side effects. Our results suggest that administering rHLH in split daily doses could provide superior results compared to the traditional single daily dose.

An investigational ovarian stimulation protocol increased significantly the psychological burden in women with premature ovarian failure.

OBJECTIVE: To assess the psychological impact (Hospital Anxiety and Depression Scale) of an investigational ovarian stimulation protocol in women with premature ovarian failure (POF). DESIGN: Prospective longitudinal study. POPULATION: Ten women with POF. METHODS: Women with idiopathic POF were placed on three consecutive treatment cycles consisting of gonadotropin ovarian stimulation after estrogen priming, gonadotropin-releasing hormone agonist pituitary desensitization, and corticosteroid immune suppression. RESULTS: Median anxiety and depression scores increased significantly from baseline following three consecutive treatment cycles from 4.0 (range 2.0-8.0) to 11.0 (range 10.0-14.0) (p-value 0.041) and from 1.5 (range 0-6.0) to 9.0 (range 7.0-10.0) (p-value 0.039), respectively. There were nine "probable" anxiety (90%) and three "probable" depression (30%) cases on the final treatment cycle compared with none (0%) on baseline (p-value 0.004 and 0.250, respectively). CONCLUSIONS: The use of investigational ovarian stimulation protocols in women with idiopathic POF was associated with excessive psychological strain. Women with POF should be cautioned against the potentially harmful aspect of similar treatments of unproven benefit.

Prevalence and determinants of complementary and alternative medicine use among infertile patients in Lebanon: a cross sectional study.

BACKGROUND: Complementary and alternative medicine (CAM) is widely used for the treatment of infertility. While the Middle East and North Africa region has been shown to house one of the fastest growing markets of CAM products in the world, research describing the use of CAM therapies among Middle-Eastern infertile patients is minimal. The aim of this study is to examine the prevalence, characteristics and determinants of CAM use among infertile patients in Lebanon. METHODS: A cross sectional survey design was used to carry out face-to-face interviews with 213 consecutive patients attending the Assisted Reproductive Unit at a major academic medical center in Beirut. The questionnaire comprised three sections: socio-demographic and lifestyle characteristics, infertility-related aspects and information on CAM use. The main outcome measure was the use of CAM modalities for infertility treatment. Determinants of CAM use were assessed through the logistic regression method. RESULTS: Overall, 41% of interviewed patients reported using a CAM modality at least once for their infertility. There was a differential by gender in the most commonly used CAM therapies; where males mostly used functional foods (e.g. honey & nuts) (82.9%) while females mostly relied on spiritual healing/prayer (56.5%). Factors associated with CAM use were higher household income (OR: 0.305, 95% CI: 0.132-0.703) and sex, with females using less CAM than males (OR: 0.12, 95% CI: 0.051-0.278). The older patients were diagnosed with infertility, the lower the odds of CAM use (p for trend <0.05). Almost half of the participants (48%) were advised on CAM use by their friends, and only 13% reported CAM use to their physician. CONCLUSIONS: The considerably high use of CAM modalities among Lebanese infertile patients, added to a poor CAM use disclosure to physicians, underscore the need to integrate CAM into the education and training of health professionals, as well as enhance infertile patients' awareness on safe use of CAM products.

Pregnancy outcomes and the effect of metformin treatment in women with polycystic ovary syndrome: an overview.

This article is a review of the literature assessing pregnancy outcomes and the effect of metformin treatment among women with polycystic ovary syndrome (PCOS). A review of research published in English was undertaken using PubMed and MEDLINE databases. The weight of the available evidence suggests that pregnant women with PCOS are at an increased risk of developing gestational diabetes, hypertensive disorders of pregnancy, preterm birth and early pregnancy loss. Obesity is a contributory factor for the increased risk of gestational diabetes in this group of women and is estimated to affect 5-40% of pregnant women with PCOS. The prevalence of other obstetric complications is estimated at 10-30% for gestational hypertension, 8-15% for pre-eclampsia and 6-15% for preterm birth. The association between PCOS and early pregnancy loss may not be direct, wherein the presence of PCOS-associated hyperinsulinemia, leading to hyperandrogenemia, has been implicated in the pathophysiology of early pregnancy loss. Apart from the role of metformin in improving the metabolic consequences accompanying PCOS, it has been shown to improve pregnancy rates in women with PCOS who are resistant to clomiphene citrate. In conclusion, pregnancy in women with PCOS is associated with adverse obstetric outcomes (multiple adverse obstetric risk). Whether metformin should be administered throughout pregnancy still remains controversial. Further prospective studies that foster a larger number of participants and adjust for all potentially confounding factors are needed.

Gynecologists' attitudes towards hormone therapy in the post "Women's Health Initiative" study era.

OBJECTIVE: To assess the impact of the Women's Health Initiative (WHI) study on gynecologists' attitudes regarding hormone therapy (HT). METHODS: Questionnaires were mailed to a random sample of Lebanese gynecologists (n=178). The questionnaires solicited practice patterns of HT for postmenopausal women and information provided while counseling before and after the WHI study. Descriptive statistical methods were used to evaluate the responses. RESULTS: Questionnaires were returned by 140 physicians (78.7%), 93.6% of whom were aware of the WHI study. More than 90% of respondents routinely offered HT prior to the study. Of the 85.6% who used a combination of oral estrogen and progesterone (E/P), 40.0% used conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA). Around 67% of gynecologists reported a change in their therapeutic approach after the study. The main changes were: not offering CEE+MPA (27.3%), prescribing CEE+MPA to a select group of patients (37.5%), using other forms of HT (56.8%), or abandoning any form of HT (6.8%). Other practice modifications included a shift to the use of tibolone (18.2%) or alternative therapies (29.5%). Whereas 76.2% of physicians counseled their patients about a decreased risk of cardiovascular events with HT prior to WHI study, only 34.1% continued to do so after the study (p<0.001). The percentage of gynecologists that inform their patients of an increased risk of breast cancer on HT rose from 45.2 to 73.2% (p=0.018). Almost 51% of gynecologists allow their patients to participate in decision making regarding the type of HT, 42.4% would choose for their patients after counseling, while 6.8% of physicians do not counsel their patients in order not to confuse them. CONCLUSION: In a representative sample of Lebanese gynecologists, there was a significant change in physicians' attitudes towards HT following the publication of the WHI study.

Perinatal outcome of vaginally delivered twin gestations with a larger twin B.

OBJECTIVE: To study the perinatal outcome of vaginally delivered twins when twin B is more than 250 g larger than twin A. STUDY DESIGN: Maternal and neonatal charts of live-born, nonanomalous twins, >25 weeks' gestation and vaginally delivered over a period of 17 years were reviewed. The results of this review were distributed among two groups: (1). those with twin B more than 250 g larger than twin A (DeltaBW>250) and (2). those where the difference was <250 g (DeltaBW<250). For vaginally delivered twin gestations, the perinatal outcome of twin B in the group DeltaBW>250 was compared to that of its co-twin, and to that of twin B in the group DeltaBW<250. RESULTS: Of the 679 twin gestations reviewed, 138 (20.6%) were in the group DeltaBW>250, of whom 73 (52.9%) delivered vaginally despite malpresentation in 39.7%. The vaginally delivered twin pregnancies in the groups DeltaBW>250 (n=73) and DeltaBW<250 (n=303) had similar demographics, parity, presentation, gestational age at delivery, and duration of the first stage of labor. Discordant twins were more frequent in the group DeltaBW>250 (26.0 versus 9.5%, p=0.001). Twin B in the group DeltaBW<250 was smaller, with higher incidence of growth restriction, low 5 min Apgar score, and hyperbilirubinemia compared to twin B in the group DeltaBW>250. There was no difference in the incidence of intraventricular hemorrhage, seizures, sepsis, neonatal death, and median nursery stay. Except for a lower median Apgar score at 1 min in twin B and a longer median nursery stay in twin A, twins A and B in the group DeltaBW>250 were similar regarding all other neonatal outcome variables. CONCLUSIONS: When twin B is more than 250 g larger than A, and both are delivered vaginally, the perinatal outcome is similar to its co-twin as well as to that of twin B of all other vaginally delivered twins. That twin B is larger than A is not itself a contraindication to attempted vaginal delivery.

Comparison of the perinatal morbidity and mortality of the presenting twin and its co-twin.

OBJECTIVE: To compare the perinatal outcome of the presenting twin to its co-twin. STUDY DESIGN: All live nonanomalous twin gestations delivered at >25 weeks' gestation between 1984 and 1994 (N=461) were identified. Twin A was compared to twin B regarding the following variables: presentation, Apgar score (AS) <4 at 1 minute, AS <7 at 5 minutes, birth weight, gender, traumatic delivery, meconium-stained amniotic fluid, cord prolapse, need for mechanical ventilation, intraventricular hemorrhage, respiratory distress syndrome, sepsis, seizures, perinatal mortality, and length of nursery stay. RESULTS: Except for differences in presentation, the perinatal outcome was similar in both twins regarding variables studied. This continued to hold true after subdividing according to mode of delivery, when infants with birth weight < or = 1500 g were considered separately, and when vaginally delivered cephalic twin A was compared to the noncephalic co-twin. However, differences in some outcome variables became evident when pregnancies with only one affected member were analyzed separately. CONCLUSIONS: When all twin pairs are considered, the outcome of the second-born twin is similar to that of the first-born regardless of the mode of delivery, presentation, or birth weight < or = 1500 g. If only those twin pairs with one affected and one unaffected twin are considered, it becomes apparent that the presenting twin is at increased risk for infection-related morbidities whereas the co-twin is at risk for other complications.