Subfertile Women Research Articles

Blood count, endocrine, immunologic, renal, and hepatic markers in a case-control animal study of induced periodontitis in female rodents.

Introduction: Periodontitis is a non-communicable chronic inflammatory disease with a systemic burden. Animal models of induced periodontitis help elucidate the mechanisms by which periodontal inflammation drives systemic effects. Studying this systemic involvement over longer follow-up periods may provide a strong foundation for future research on the association between diseases and periodontitis, particularly in female rats. Therefore, we aimed to compare blood, endocrine, immunologic, renal, and hepatic markers in a rat model of induced periodontitis in females with their control counterparts. Methods: Experimental periodontitis was induced in 20 female Wistar rats by the application and maintenance of silk ligatures on the upper molars. The rats were then assessed for macroscopical analysis, complete blood count, and biochemical, endocrine, and immunologic markers at 21, 28, 42, and 56days. Results: Chronic periodontal inflammation was observed after 42days of exposure to the ligatures. Additionally, it was also possible to notice significant systemic manifestations, such as the reduction of triiodothyronine and thyroxine levels, along with an increase in the expression of alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase. Discussion: The study's findings imply that certain changes can be underscored to highlight a reduced risk of conception. Notably, previous investigations have indicated that subfertile women exhibit lower levels of thyroid hormones and elevated lactate dehydrogenase expression. Despite the absence of preclinical data delineating a possible association between periodontitis and female infertility, the results of this study may prove to be a crucial contribution to both the scientific and medical fields.

Endometriosis diagnosed by ultrasound is associated with lower live birth rates in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection treatment

ObjectiveTo study the cumulative live birth rate (CLBR) after the first In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) treatment in women with or without deep infiltrating endometriosis (DIE) and/or endometrioma diagnosed by transvaginal ultrasonography (TVUS), using the International Deep Endometriosis Analysis (IDEA) group definitions. DesignProspective observational cohort study at a university hospital. SubjectsIn total 1040 subfertile women aged 25- ≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. Of these, 234 (22.5%; 95% Confidence Interval (CI), 20.0 – 25.0) women were diagnosed with DIE and/or endometrioma at systematic TVUS prior to starting their treatment. ExposureAll women underwent their first IVF or ICSI treatment. Fresh and/or frozen embryos from the first cycle were used until pregnancy was achieved or no embryos remained. Main Outcome MeasuresCLBR after the first IVF/ICSI cycle in women with or without DIE and/or endometrioma. ResultsThe CLBR after the first IVF/ICSI treatment in the total cohort of women was 426/1040, (41.0%; 95% CI, 38.0 – 44.0). Women with DIE and/or endometrioma had a lower CLBR (78/234, 33.3%; 95% CI, 27.3 – 39.4) compared to women without the disease (348/806, 43.2%; 95% CI, 39.8 – 46.6), p=0.007. The crude relative risk (RR) for cumulative live birth for women with DIE and/or endometrioma was 0.77; 95% CI, 0.63-0.94, and after adjustments were made for age, BMI, s-anti müllerian hormone, stimulation protocol and day for embryo transfer, the adjusted RR was 0.63; 95% CI, 0.48-0.82. There was no difference in the number of retrieved mature oocytes, fertilization rate or good quality embryos between the two groups. ConclusionThe presence of DIE and/or endometrioma diagnosed by TVUS lowers the chance for a live birth in women undergoing their first IVF/ICSI treatment.

Stimulation protocols for Severe Endometriosis- is there any difference?

Endometriosis, being an estrogen-dependent condition, can lead to subfertility in women. Those facing difficulty achieving pregnancy goals may need assistance from assisted reproductive technology (ART). Due to the challenges posed by endometriosis in natural conception, assisted reproductive technologies like IVF and ICSI. Objective of the study: This study aimed to compare ART outcomes in women with endometriosis following the three distinct groups of protocols undergoing various treatment modalities, namely the progestin-primed ovarian Stimulation protocol, GnRH agonist long protocol, and Combined Oral Contraceptives (OCPs). This investigation aims to enhance our understanding of how different stimulation protocols may influence ART outcomes Methodology: This is a cross-sectional study between March 2019 to March 2023. The study collected data from 126 infertile women diagnosed with endometriosis, who were undergoing their first intracytoplasmic sperm injection (ICSI) cycle at MHRT Hospital and Research Center, Hyderabad, Telangana India. Patients in each group were classified into three Protocols ie-GnRH agonist Long Protocol, Progestins primed Ovarian Stimulation, and Combined Oral Contraceptives. The outcomes of the ICSI program were evaluated Result: The findings from our study suggest that women with endometriosis undergoing ICSI experience improved reproductive outcomes when subjected to prolonged downregulation with GnRH agonist long protocol, Progestin primed Ovarian Stimulation and Combined Oral Contraceptives before initiating ovarian stimulation. Notably, the clinical pregnancy rate is notably higher at GnRH agonist long Protocol 57.5% compared to the alternative protocols: PPOS at 34.2 % and Combined Oral Contraceptives at 40.54 %. The groups subjected to extended pituitary downregulation with GnRH agonists long protocol demonstrated superior clinical pregnancy and live birth rates compared to those following the PPOS and Combined Oral Contraceptives. Our segmented IVF approach, including FET cycles, revealed a higher live birth rate in the GnRH agonist protocol compared to the PPOS and Combined Oral Contraceptives. Conclusion: This study demonstrates that GnRH agonists' long protocol demonstrated superior clinical pregnancy and live birth rates compared to those following the PPOS and Combined Oral Contraceptives. Better clinical outcomes were observed in the GnRH agonist long protocol group when compared to the PPOS and Combined Oral Contraceptive group.

'Age specific variations in ovarian reserves in healthy fertile and infertile women: A cross sectional study.

Ovarian reserve tests are valuable for evaluation of female fertility, and to formulate appropriate treatment strategies for infertile women. Antral follicle count (AFC) and Anti-Mullerian hormone (AMH) are most reliable markers of ovarian reserve which are related inversely to age. There are many factors that affect ovarian reserve like race, ethnicity, fertility status, BMI or any chronic illness. We conducted this study to find outage specific nomograms for AMH and AFC among fertile and Infertile Indian women, to find out any variations between fertile and Infertile ovarian reserves at various centiles, to define the age cut-off of decline in AMH and AFC among fertile and Infertile Indian women and to find correlation between AMH and AFC. It was a prospective cross sectional single centre study conducted at a tertiary hospital of northern India from March 2017 to February 2022. Fertile healthy women were recruited from family planning clinic, oocyte donors and subfertile women from Gynaecology and ART clinic. AMH was done using ELISA, Beckmann Coulter Gen II assay and AFC was done using TVS with high frequency probe (9.0 MHZ, Voluson,S-6, GE Healthcare, USA) by trained personnel. R Statistical Programming Language was used for statistical modelling and visualization. Age-specific AFC centile chart and AMH centile chart were generated using GAMLSS (Generalized Additive Models for Location Scale and Shape) package available in R Statistical Computing Language. A Non-linear decline in ovarian reserves among fertile, while linear among infertile women was seen. Centiles defined for both groups with a faster decline in infertile women. Age cut off for decline in AMH and AFC in fertile women approximately 31 years using ROC analysis and Age cut off for decline in AMH and AFC in infertile women is approximately 34 years. There seems to be a good correlation between AFC and AMH. We need to counsel women to consider child bearing well before ovarian reserves decline (31-34 years).

Detection of uterine abnormalities using three-dimensional vaginal ultrasound in infertile women undergoing assisted reproductive techniques

Abstract Background: Uterine shape and cavity abnormalities form a common cause of subfertility, for which thorough assessment is considered as a core part in infertility evaluation. A variety of modalities (invasive and none invasive) such as hysterosalpingography, transvaginal sonography, diagnostic hysteroscopy, two-dimensional hysterosonography, and three-dimensional hysterosonography can be used for the diagnosis of uterine abnormalities. Objectives: To address the detection rate of uterine and endometrial abnormalities in infertile women undergoing assisted reproductive techniques (ART) using three-dimensional vaginal ultrasonography. Materials and Methods: A cross-sectional observational study that involved 211 subfertile women who were arranged to undergo ART for different causes of infertility. After taking their verbal consent for participation in this study, all women examined by 2D vaginal U/S for initial assessment of their pelvic anatomy then followed by three-dimensional U/S with or without saline infusion for further assessment of the uterine and endometrial cavity morphology. Women with ultrasound detected endometrial abnormalities further underwent hysteroscopic assessment, histopathological specimens were taken and were treated as recommended by their gynecologist. Results: Twenty-two percent of the studied group discovered to have uterine and/or endometrial abnormalities including endometrial polyps and uterine myomas are the most commonly detected abnormalities while congenital uterine malformation detected in 3.8% of the total patients using three-dimensional ultrasonography. Conclusion: Uterine and endometrial abnormalities are common in subfertile patients, the prevalence of uterine and endometrial abnormalities (endometrial polyps or irregularities, uterine myomas including submucous one) was 22%, whereas congenitally maldeveloped uteri were detected in 3.8% of women undergoing ART (using 3D U/S) which may have a negative impact on ART outcome.

Prevalence of Diminished Ovarian Reserve in Sub-fertile Women Under 40 years of Age

Background: Diminished ovarian reserve defined as when woman ovaries lose their reproductive potential in terms of quality and quantity of eggs leading to reduced fecundability and poor ovarian response to stimulation. Female age is most common prognostic element but diminished ovarian reserve is quite common under 40 years old young sub-fertile women. It is best assessed by hormonal tests like FSH and AMH levels. Objective: To assess the prevalence of diminished ovarian reserve among sub-fertile women under 40 years age. Study Design: Cross sectional study. Settings: Department of Obstetrics and Gynecology, Mufti Mehmood Hospital, Dera Ismail Khan Pakistan. Duration: One year from January 01, 2022 to December 31, 2022. Methods: After meeting the inclusion criteria 593 sub-fertile women were enrolled. FSH level was performed on day 2 or 3 of menstrual cycle. if found more than 10 IU, it was repeated 4 to 6 weeks apart to satisfy the criteria of poor ovarian reserve. The primary outcome was to find the prevalence of diminished ovarian reserve in local population and secondary outcome was to assess the frequency of menstrual cycle pattern and type of subfertility in these women. The prevalence of diminished ovarian reserve and in respect to different age groups, menstrual cycle patterns like oligomennohoea, and type of infertility (primary or secondary) were presented with frequency percentages. Results: The mean age of the females was 35.98 years with 84 ((68%) women in age group 36-40.15 woman (12.29%) had amenorrhea of less than 4 months.62(50.8%) had oligomenorrhoea with scanty flow while 45(36. 6 %) had regular menstrual cycle with normal flow or scanty flow. 92 women (75.4%) had primary infertility while 30 (24.5%)had secondary infertility. Conclusion: The prevalence of diminished ovarian reserve was 20%among sub-fertile women under 40 years age with mean age of 35.98 years with highest prevalence in age group 36- 40 years. Oligomenohoea with scanty flow was the commonest menstrual pattern with more common primary subfertility.

Inositol - why should it be in the spotlight for women in a reproductive age?

Introduction and purpose: Inositol exists in the form of nine isomers, two of which are dominant - myo-inositol (MI) and D-chiro-inositol (DCI). It is a naturally occuring sugar involved in many biological pathways. Due to its insulin-sensitizing, anti-inflammatory and antioxidant properties, inositol has been suggested as a novel treatment agent in prevention and treatment of reproductive disorders. The paper presents currently available data regarding the impact of oral supplementation of inositol for fertility of women and men, reproductive outcomes among subfertile women with polycystic ovarian syndrome (PCOS) and its effectiveness on preventing and treating gestational diabetes mellitus (GDM).
 Material and methods of research: The search was conducted using PubMed and Google Scholarship databases available to November 2023. 
 Results: Although the evidence is still insufficient, it is suggested that inositol may be beneficial for subfertile women, also those undergoing assisted reproductive techniques and in vitro fertilization. Moreover inositol can positively influence sperm quality. Myoinositol supplementation was also effective and safe for pregnant women with GDM and their children. In these women lower HOMA-IR (Homeostatic Model Assessment – Insulin Resistance) and reduction of fetal macrosomia were observed. Myoinositol also seems to be favorable for overweight or obese women in GDM prevention and treatment. Current findings indicate the positive impact for hormonal changes and restoration in menstrual cyclicity in women with PCOS, improving reproductive disorders in these patients.
 Conclusions: Overall, although findings are encouraging, further trials for this promising intervention are still required to support oral supplementation of inositol.

Ambient traffic related air pollution in relation to ovarian reserve and oocyte quality in young, healthy oocyte donors

Studies in mice and older, subfertile women have found that air pollution exposure may compromise female reproduction. Our objective was to evaluate the effects of air pollution on ovarian reserve and outcomes of ovarian stimulation among young, healthy females. We included 472 oocyte donors who underwent 781 ovarian stimulation cycles at a fertility clinic in Atlanta, Georgia, USA (2008–2019). Antral follicle count (AFC) was assessed with transvaginal ultrasonography and total and mature oocyte count was assessed following oocyte retrieval. Ovarian sensitivity index (OSI) was calculated as the total number of oocytes divided by total gonadotrophin dose × 1000. Daily ambient exposure to nitric oxide (NOx), carbon monoxide (CO), and particulate matter ≤ 2.5 (PM2.5) was estimated using a fused regional + line-source model for near-surface releases at a 250 m resolution based on residential address. Generalized estimating equations were used to evaluate the associations of an interquartile range (IQR) increase in pollutant exposure with outcomes adjusted for donor characteristics, census-level poverty, and meteorological factors. The median (IQR) age among oocyte donors was 25.0 (5.0) years, and 31% of the donors were racial/ethnic minorities. The median (IQR) exposure to NOx, CO, and PM2.5 in the 3 months prior to stimulation was 37.7 (32.0) ppb, 612 (317) ppb, and 9.8 (2.9) µg/m3, respectively. Ambient air pollution exposure in the 3 months before AFC was not associated with AFC. An IQR increase in PM2.5 in the 3 months before AFC and during stimulation was associated with −7.5% (95% CI −14.1, −0.4) and −6.4% (95% CI −11.0, −1.6) fewer mature oocytes, and a −1.9 (95% CI −3.2, −0.5) and −1.0 (95% CI −1.8, −0.2) lower OSI, respectively. Our results suggest that lowering the current 24-h PM2.5 standard in the US to 25 µg/m3 may still not adequately protect against the reprotoxic effects of short-term PM2.5 exposure.

Laparoscopic and hysteroscopic findings in women with sub-fertility and tuberculosis: A case series.

Evaluation of hysteroscopic and laparoscopic findings in subfertile women predictive of tuberculosis. Retrospective case series analysis. Tertiary hospital in India. A retrospective analysis of 16 784 subfertile women who had undergone diagnostic hysterolaparoscopy (DHL) was conducted between February 2014 and June 2021. Histopathological evidence, acid-fast bacilli (AFB), culture and GeneXpert MTB/RIF assay were used to diagnose female genital tuberculosis (FGTB). Various hysteroscopic and laparoscopic findings were analysed, and a binary logistic regression assessed associations between these findings and positive diagnostic outcomes. Various hysteroscopic and laparoscopic findings correspond to tubercular manifestation. Of the 16,784 patients, 1083 had hysteroscopy and laparoscopy findings suggestive of tuberculosis, and 309 were diagnosed with FGTB based on diagnostic tests. Logistic regression identified variables strongly predictive of positive status outcomes; tuberculous abdomino-pelvic adhesions of various grades, isthmo-ampullary block, tubercle, tubo-ovarian mass, tuberculous hydrosalpinx, complete tubal destruction, tubal diverticula and rigid tube emerged as strong predictors. Logistic regression-derived predictors, alongside specific laparoscopic and hysteroscopic findings, can enhance diagnostic accuracy and clinical decision-making to start antitubercular therapy in subfertile women.

Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy.

Non-Lactobacillus-dominated vaginal microbiota has been associated with poor gynecologic health and complications during pregnancy. Lactobacilli and especially Lactobacillus crispatus associate with good reproductive health and dominate the microbiota during healthy pregnancy. We examined whether the composition of vaginal microbiota at the time of fresh embryo transfer (ET) has an impact on the success of in vitro fertilization (IVF) and whether vaginal microbiota changes from IVF-ET to early pregnancy within individuals. Vaginal swab samples were collected from subfertile women at the time of IVF-ET (n = 76) and at the eighth gestational week (n = 21) from those who achieved clinical pregnancy. The microbiota composition was analyzed using 16S rRNA gene amplicon sequencing. L. crispatus was more abundant among the 30 women who achieved clinical pregnancy (46.9% vs. 19.1%, q = 0.039) and the 26 women who had live birth (43.3% vs. 23.1%, q = 0.32) compared to those who did not. Lactobacilli, mainly L. crispatus (76.2%), dominated all early pregnancy samples. Microbiota remained the same, i.e., Lactobacillus-dominated type in 52% (11/21), shifted from one Lactobacillus-dominated type to another in 24% (5/21), or shifted from mixed community to Lactobacillus-dominated type in 24% (5/21) women, but never from Lactobacillus dominance to non-lactobacilli dominance. Our results emphasize the role of L. crispatus in the success of IVF-ET and in early pregnancy. During pregnancy, the microbiota shifted toward L. crispatus dominance even if it was undetectable before pregnancy, indicating that most women hold a reservoir of this beneficial Lactobacillus in their reproductive tract.IMPORTANCEInfertility is a global public health issue which leads many couples to seek fertility treatments, of which in vitro fertilization (IVF) is considered to be the most effective. Still, only about one-third of the women achieve live birth after the first IVF embryo transfer (IVF-ET). Factors affecting embryo implantation are poorly known, but the female reproductive tract microbiota may play a key role. Our study confirms the beneficial role of vaginal lactobacilli, especially Lactobacillus crispatus, in the probability of achieving clinical pregnancy and live birth following IVF-ET. Our findings regarding the intra-individual shift of vaginal microbiota between non-pregnancy and pregnancy states are novel and provide new information about the dynamics of microbiota in the early steps of human reproduction. These findings may help clinicians in their attempts to optimize the conditions for ET by microbiota screening or modulation and timing the ET when the microbiota is the most favorable.

FRI420 Prevalence Of Ovarian Hormone Suppression Is High Among Regularly Cycling Reproductive-aged Women With Overweight Or Obesity

Abstract Disclosure: A. Caldwell: None. A.J. Polotsky: None. A.P. Bradford: None. H. Smyth: None. K. Kuhn: None. J. Siegart: None. N.F. Santoro: Advisory Board Member; Self; Astellas Pharma, Menogenix Inc., Que Oncology, Project Ember/Amazon. Grant Recipient; Self; Menogenix Inc. Other; Self; Ansh Labs Scientific Consultant. V.A. Catenacci: None. Endo Abstract Background: The prevalence of ovarian hormone suppression in regularly cycling, pre-menopausal women with overweight or obesity (termed relative hypogonadotropic hypogonadism of obesity) is not fully appreciated, as there are no overt symptoms aside from subfertility in women trying to conceive. In addition to impacting fertility, ovarian hormones play an important role in energy homeostasis and fat distribution. Other states characterized by ovarian hormone suppression (polycystic ovarian syndrome, PCOS and menopause) are associated with increased cardiometabolic disease risk. It is therefore critical to have a better understanding of the prevalence of ovarian hormone suppression in women with overweight or obesity. Methods: We compared cycle length and ovarian hormones in pre-menopausal women (age 18-40) who had regular menstrual cycles, no history of PCOS or diabetes, and were not using hormonal birth control (currently or in the past 3 months) and were either with overweight or obesity (OW/O, BMI 27-40 kg/m2, n=23) or healthy weight (HW, BMI 18-25kg/m2, n=15). Both groups provided daily, first-morning voided urine samples over a complete menstrual cycle. Progesterone and estrogen metabolites were assayed (pregnanediol-3-glucuronide [Pdg], estrone-1 conjugates [E1c]; Centaur CP; Siemens) and adjusted for creatinine. Hormones were assessed using whole cycle area under the curve (AUC) measurement. Ovarian hormone suppression was defined a priori as Pdg AUC < 25th percentile of the HW control group. T-tests and Spearman correlations were used to compare groups and examine associations between hormones and BMI. Mean±SD are presented. Results: Cycle length was not different between groups, but BMI (OW/O: 34.3±5.3, HW: 21.6±1.3 kg/m2) and age (OW/O: 34.6±5.3, HW: 29.2±4.2 years) were (p < 0.01), thus all analyses controlled for age. Pdg was significantly lower (p<0.01) in OW/O (AUC = 21.29±13.98 ug/mg Cr) relative to HW (AUC = 39.13±22.20 ug/mg Cr) and the majority (82.6%) of the OW/O women exhibited ovarian hormone suppression. E1c was also significantly lower (p<.0001) in the OW/O (AUC = 384.8±211.4 ng/mg Cr) group relative to HW (AUC = 1740.00±627.20 ng/mg Cr). Across the full sample, there were negative correlations between BMI and Pdg AUC (rpartial = -0.34, p = .03) and BMI and E1c AUC (rpartial = -0.61, p < .0001). Conclusion: Ovarian hormone suppression was observed in a majority of our sample of pre-menopausal women with overweight or obesity. Despite the difficulty of identifying this phenotype clinically, it may have important implications for weight management and cardiometabolic disease risk, in addition to fertility, and warrants further investigation to improve women’s health during the reproductive lifespan and beyond. Presentation: Friday, June 16, 2023

Adverse pregnancy outcomes in twins and their association with the conception method

Assisted reproductive technology (ART) has given the opportunity of conception to a large proportion of subfertile women and, at the same time, has led to a substantial increase of multiple pregnancies. Several studies have shown that in vitro fertilization conceived twin pregnancies carry a significant risk of perinatal morbidity and complications. However, it remains unknown whether IVF per se actually increases the risk of pregnancy complications in twin pregnancies or if these should be attributed to the maternal characteristics. In the present review we summarize the findings of published studies related to the most common pregnancy complications encountered in IVF conceived twin pregnancies.

Outcomes of the Next In Vitro Fertilization Cycle in Women with Polycystic Ovary Syndrome after a Failed In Vitro Maturation Attempt.

In vitro maturation (IVM) is indicated in women with polycystic ovary syndrome (PCOS) who have a very good ovarian response during in vitro fertilization (IVF) and are therefore at high risk of ovarian hyperstimulation syndrome (OHSS). According to the latest practice committee document, IVM could be a major advance in assisted reproductive technology (ART) procedures (reduced cost and simplified treatment); nevertheless, retrospective studies of IVM versus IVF still demonstrate lower chances of a live birth with IVM. Could IVM prove to be an optimal first-line treatment approach? And limited information is available concerning the success of the subsequent IVF cycle after the failure of an IVM cycle. Does IVM treatment adversely affect the subsequent IVF cycle, and is this worth considering before performing the IVF cycle for women with PCOS? This prospective nested case-control study at the Peking University Reproductive Medicine center in China was performed between March 2018 and September 2020. Women aged 20-38 years with PCOS and infertility and who were scheduled for their first IVF attempt were eligible. A total of 351 women were randomly allocated to receive one cycle of unstimulated natural IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol followed by hCG as an ovulation trigger (n = 176). This study involved 234 women (58 women with no blastocysts in the first IVM cycle and 158 women who underwent the first IVF cycle). Cumulative live birth rate at 12 months after oocyte retrieval and OHSS of a standard controlled ovarian stimulation (COS) IVF cycle were compared between 58 women in an IVF cycle following a failed IVM cycle and 158 women who underwent the first IVF cycle. No significant differences were found in the cumulative live birth rate (CLBR), ongoing pregnancy rate, or clinical pregnancy rate at 12 months after oocyte retrieval between the two groups (56.9% vs. 58.9%, p = 0.795; 58.6% vs. 60.8%, p = 0.776; and 84.5% vs. 76.0%, p = 0.178). The incidence of moderate-to-severe OHSS was not significantly different between the groups (6.9% vs. 5.7%, p = 0.742). Additionally, there were no significant differences in the total gonadotropin dose, stimulation duration, number of retrieved oocytes, number of retrieved mature oocytes, or fertilization rates. Even if the first IVM attempt failed in subfertile women with PCOS, comparable cumulative live birth rates were observed in the subsequent IVF cycle. IVM treatment does not adversely affect the subsequent IVF cycle.

Fertility and Obstetric Outcomes of Assisted Reproductive Technology (ART) in Women With Adenomyosis Following Gonadotropin-Releasing Hormone Agonist Therapy: A Single-Center Experience.

Adenomyosis is an ambiguous disorder causing a wide variety of implications from dysmenorrhea, heavy menstrual bleeding, and infertility to pregnancy complications. Adenomyosis is associated with altered endocrine and inflammatory milieu, resulting in impaired implantation and reduced fertility potential. It is also associated with increased incidence of obstetric complications such as miscarriage, antepartum hemorrhage, placental mal-position, hypertensive disorders, small for gestational age-intrauterine growth restriction (SGA-IUGR), cesarean section, preterm labor, preterm premature rupture of membranes (PPROM), and neonatal intensive care unit (NICU) admissions. The aim of our study was to investigate the fertility and obstetric outcomes in women with adenomyosis treated with GnRH agonists compared to controls with normal uteri undergoing in-vitro fertilization (IVF) at our center, thereby establishing the role of gonadotropin-releasing hormone (GnRH) agonists in managing sub-fertile women with adenomyosis. We carried out a retrospective cohort study at our hospital to analyze the effects of adenomyosis on IVF and pregnancy outcomes. This study (n=83) involves women with adenomyosis between the ages of 21 and 37 years who were followed up at our center between 2013 and 2022. The controls (n=83) were selected from women who underwent IVF-intracytoplasmic sperm injection (IVF-ICSI) for tubal or mild male factor infertility with normal appearing uterus within the same time frame. Women with adenomyosis were given GnRH agonist as long/ultralong agonist protocol before controlled ovarian stimulation or as down-regulated frozen embryo transfer (FET). The length of suppression was between one and six months based on the size of the uterus and response to treatment. Fertility and obstetric outcomes were analyzed. The implantation rates were found to be equivocal: 54.2% and 53% in the adenomyosis and control groups, respectively (p=0.208). The cumulative live birth rate was 50.6% and 48.2% in the study and control groups,respectively (p=0.341). The biochemical pregnancy rate and the first- and second-trimester miscarriage rates were not significantly different between the group with adenomyosis and the group with normal uterus. The incidence of preterm deliveries and antepartum hemorrhage was found to be significantly increased in the study group. Medical management in women with adenomyosis optimizes the live birth rates giving results at par with the control population.

Ovarian reserve analysis in subfertile women based on physical, ultrasound and hormonal parameters

Purpose : Despite the availability of several markers for the evaluation of ovarian reserve, the correlation between the markers has not been reported clearly in the existing studies. Therefore, this study investigated the level of subfertility by comparing the physical parameters such as age and BMI in the subfertile women. In addition, the study compared the ultrasound and hormonal parameters with the physical parameters in subfertile women. Methods : A total of 200 subfertile patients presented to outpatient department were considered in this study. The selected candidate was 29 to 39 years old and was investigated after two years of unprotected sexual intercourse. A consecutive enumerative sampling method has been employed for data collection. The collected data are processed to determine correlation and regression coefficients using Statistical Package for Social Sciences (SPSS) version 20.0. Results : The results revealed that follicle stimulating hormone (FSH) level and anti-Mullerian hormone (AMH) values varied among the above 30 age group of respondents with BMI values 25–30. There is no relationship between the respondents’ right and left ovarian volume by comparing age within BMI. Conclusion : In conclusion, there is a strong relationship between the FSH level, AMH and physical parameters age and BMI. The reproductive age of women will be older than or younger than the actual age of the women. The reproductive age will be calculated with the ovarian volume, ovarian reserve, ovary size and time to menopause.

P-753 Preferences in subfertile women for hysterosalpingography or transvaginal hydrolaparoscopy in the fertility work-up: a labelled discrete choice experiment.

Abstract Study question What aspects do subfertile women prefer for hysterosalpingography (HSG) or transvaginal hydrolaparoscopy (THL) to assess their Fallopian tubes? Summary answer The chance of a false negative result, failure rate, and waiting time are attributes that impact women’s preference for tubal patency testing strategy. What is known already THL and HSG are commonly used diagnostic tests for tubal patency testing, both with different features. HSG is a radiological procedure whit contrast to evaluate tubal patency, whereas THL is a procedure where access to the pouch of Douglas is obtained with an endoscope and the tubes are tested with methylene blue. THL was found non-inferior to HSG as a first-line test in terms of conception leading to live birth. Until now, limited research has been performed to study the values and preferences of subfertile women in the diagnostic work-up. Study design, size, duration We conducted a labelled discrete choice experiment (DCE), which is an attribute-based survey method for measuring preferences. This DCE consisted of 2 questionnaires with each 12 different choice sets. Women with an indication for tubal patency testing were included in the study between September 2021 and January 2023 in two Dutch hospitals. They were randomly assigned for questionnaire 1 or 2. Participants/materials, setting, methods Attributes were defined based on literature review, structured patient interviews and expert focus groups. This resulted in five final attributes: the chance of having a “false negative” result, complication rate, failure rate, subsequent management after a failed procedure and waiting time. Women were asked to choose between choice sets with hypothetical scenarios of two tubal patency tests with different levels of the attributes. Data were analysed by using multinomial logistic regression. Main results and the role of chance The questionnaire was returned by 75 out of 80 women. Mean age was 31.8 years and mean duration of subfertility was 23.5 months. 65 women experienced primary subfertility vs 10 who experienced secondary subfertility. For THL women preferred a lower chance of a false negative result (p < 0.001), a lower failure rate (p = 0.008) and a shorter waiting time (p = 0.003). Outcomes for chance of complications and management after a failed procedure were not significant. Only for the group of women with primary subfertility, if a THL is not conclusive or if there is a failure to reach the pouch of Douglas, women prefer to have a conventional laparoscopy over expectant management (p = 0.01). Women choosing HSG preferred a lower chance of a false negative result (p < 0.001), a shorter waiting time (p = 0.02) and a lower chance of complications (p = 0.001). Because of the labelled design we performed, we saw that women chose for THL significantly more than for HSG; 83% vs 17% (P = 0.03). This may be caused by way of counselling and the fact that these medical centres are one of the few centres in the Netherlands that perform the THL. Limitations, reasons for caution Our analysis with 78 women, showed significant outcomes in terms of preference on specific attributes, but it is possible that we would have found stronger associations with a larger sample size. Wider implications of the findings These results provide more insight in the perspective of subfertile women about the aspects of tubal patency testing in the fertility work-up and they enable informed decision making. Further research is needed to compare our findings to the other forms of tubal patency testing in the fertility work-up. Trial registration number N20.009

O-094 Management of subfertility in women with PCOS: expectations, problems and solutions

Abstract Polycystic ovarian syndrome (PCOS) is a common cause of subfertility particularly when anovulation is present. In this circumstance efforts are made to induce ovulation through lifestyle modification, medication, or a combination of both. Other patients with PCOS may be ovulatory but require IVF/ICSI for other causes, including male factor or tubal infertility. In all cases, attention needs to be placed on the underlying metabolic, psychological, and reproductive features that may complicate treatment and subsequent pregnancy. Pregnancy itself has a higher chance of complications and these can be reduced by adequate preconception evaluation and intervention. Recently, the international evidence-based guideline for evaluation and treatment of PCOS has been updated (1) and the infertility section subjected to a literature integrity check to exclude publications that did not meet the highest criteria for incorporation into clinical management. A recent individual patient data meta-analysis has also clarified the relative efficacy of fertility treatments (2). The following conclusions are recommended; 1. Letrozole is the first line drug of choice for ovulation induction based on its efficacy and lower multiple pregnancy rate 2. Clomiphene is an effective drug particularly given a long experience of use and its lower cost 3. Metformin may be valuable for some patients particularly if glucose intolerance is present 4. A combination of clomiphene and metformin may be effective, particularly in overweight individuals 5. Gonadotrophins are an effective treatment in experienced clinics which the resources to undergo adequate monitoring 6. Laparoscopic ovarian surgery may assist some patients and is associated with a lower multiple pregnancy rate and may have long term benefits 7. IVF may be safely conducted with appropriate safeguards to reduce ovarian hyperstimulation syndrome in those where ovulation induction has failed. It should be noted that some of these drugs are “off-label” in many countries and are not recommended in several healthcare systems.There are several areas where further information may lead to altered and improved practice: 1. IVF as a first line therapy may be more effective and allow better control of multiple pregnancy rates. 2. In vitro maturation (IVM) with IVF/ICSI shows increasing success with no or minimal FSH use (3). 3. Bariatric surgery is more readily available and may lead to significant weight loss related ovulation. 4. Newer GLP1 receptor agonists show dramatic weight loss and are being evaluated in PCOS. 5. First line gonadotrophin treatment has been advocated by some proponents. 6. Higher dose and longer use of standard oral agents may help in ovulation induction resistant patients. 7. Inositol and myoinositol are being evaluated as safe, low cost, over the counter alternatives. 8. Alternatives to hCG are available for ovulation induction in oral and IVF cycles. 9. Promising pharmacogenomic approaches may allow individualisation of treatment. While the genomic and environmental aetiology of PCOS remains uncertain, the increasing emphasis on evaluation and assessment of effective therapies for subfertility is advancing rapidly.

P-482 Bacterial vaginosis in a subfertile population undergoing fertility treatments: a prospective cohort study

Abstract Study question Does bacterial vaginosis (BV) influences pregnancy rates during fertility treatments? Summary answer BV does not significantly impact ongoing pregnancy or live birth rates but could affect miscarriage rates. What is known already BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect of BV on fecundity especially in the in vitro fertilisation (IVF) population. Study design, size, duration Observational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination (IUI) or IVF. Participants/materials, setting, methods Participants undergoing IUI, IVF or intra cytoplasmatic sperm injection (ICSI). Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiome analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations (GEE) analysis was used to account for multiple observations per couples. Main study outcome was defined as ongoing pregnancy at 12 weeks. Secondary outcomes were miscarriage rate and live birth rate. Main results and the role of chance A total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV-status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type (CST). There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or microbiome CST group III/IV. Sample outcomes of qPCR BV were in accordance with their microbiome analyses. On baseline groups significantly differed on smoking status and body mass index (BMI). Odds ratios were adjusted for smoking status, BMI and socioeconomic status. Limitations, reasons for caution Numbers of the initial sample size calculation were not met. Therefore, numbers may be too small to draw firm conclusions. Wider implications of the findings This study describes the influence of BV or an abnormal microbiome in a subfertile population undergoing fertility treatments. A possible effect of lifestyle factors on BV-status is shown. Combining qPCR and microbiome results and analysing both IUI and IVF/ICSI treatments can contribute to better generalisability to the consulting room. Trial registration number Z21.031

P-779 School performance of children conceived by assisted reproductive technology

Abstract Study question Does elementary school performance differ between children conceived through assisted reproductive technology (ART) compared to children born to subfertile couples not conceived by ART? Summary answer Children born after ART perform equally well at age 12 (end of elementary school) compared to children born to subfertile couples not conceived by ART. What is known already It is well established that pregnancies conceived by ART are at higher risk of adverse outcomes, such as pre-term birth and a lower birth weight, also when restricted to singleton pregnancies. However, whether ART also affects outcomes in later life, such as school performance, is less clear. Although some studies indicate that there might be subtle differences in the school performance of ART and spontaneously conceived children, it remains unclear whether this is due to the ART treatment, parental factors or a combination of both. Study design, size, duration Data were used from the OMEGA-cohort, a historical nationwide cohort with prospective follow-up in the Netherlands. The cohort comprises all offspring of women who were treated in one of the 13 IVF clinics or 2 regional fertility centers in 1983-2010. Of 89,249 live-born children, 54,417 were ART-conceived and 37,832 were not ART-conceived (conceived naturally with or without ovarian stimulation) by subfertile women. Participants/materials, setting, methods Data on type of fertility treatment and maternal risk factors were available from medical records of the mothers and through the national perinatal registry. The OMEGA-cohort was linked to the education dataset of Statistics Netherlands, including school performance data for the period 2006-2017, leaving 24,806 children in the analytical cohort. The overall test Z-score and Z-scores on the separate domains (Dutch language and mathematics) between ART and non-ART children were compared using multivariable linear regression. Main results and the role of chance The cohort comprises 14,958 ART-conceived children and 9,848 non-ART children with test scores around age 12 in 2006-2017. The mean overall score was 536,5 (SD = 9.7), with scores of 536.4 (SD = 9.9) in ART-conceived children and 536.6 (SD = 9.5) in non-ART children. After adjustment for maternal age and maternal and paternal educational level, in a multivariable linear regression model, the overall test Z-score was also not different among ART-children compared to non-ART children from subfertile parents (β=-0.02, 95% CI=-0.04-0.01). Overall test Z-scores were not different according to different ART treatment modalities, IVF (β=-0.02, 95%CI=-0.05-0.01), ICSI (β=-0.01, 95% CI=-0.05-0.02) and frozen embryo transfer (β = 0.07, 95%CI=-0.01-0.14) when compared to children born to subfertile couples not using ART. ART children performed equally well on mathematics and Dutch language compared to children born to subfertile couples not conceived by ART. Limitations, reasons for caution Although the current analyses include a large proportion of the ART children in the Netherlands with data on school performance and our study had sufficient power to address the research question, it is not clear to which extent our results are generalizable to other countries. Wider implications of the findings Reassuringly, based on first results, children born after ART had comparable test scores at the end of elementary school compared to children from subfertile couples not conceived by ART. Trial registration number Not applicable

P-258 In-vitro oocyte maturation (IVM) in the ART clinic – What can we learn from our failed cycles?

Abstract Study question Why do some IVM cycles remain unsuccessful? Which factors contribute to failure in producing a usable embryo in IVM cycles? Summary answer Failure to obtain usable embryos after IVM was associated with oocyte dysfunction, inappropriate patient selection and unanticipated low oocyte yield. What is known already In-vitro maturation of oocytes retrieved from antral follicles has been offered as a mild-ART-approach to subfertile women with increased functional ovarian reserve, ovarian resistance to gonadotropins and in the context of fertility preservation. When using monophasic IVM culture systems, oocyte maturation, embryological development and pregnancy outcomes are generally lower compared to conventional ART (cART). Women who yield high numbers of cumulus oocyte complexes from a single egg retrieval procedure, such as those with polycystic ovary syndrome (PCOS), have been considered the best candidates for IVM, to compensate for the lower maturation rate and lower embryo yield from IVM cycles. Study design, size, duration This was a single-tertiary center, retrospective cohort study between May 2018 and February 2022 including 277 patients: 53 patients with failed IVM and 224 patients with a successful IVM cycle (inter-patient analysis). All ART cycles from patients with one failed IVM were investigated (intra-patient analysis). Failed IVM cycles were grouped: (i) ≤20% oocyte maturation; (ii) fertilization failure; (iii) embryo development failure. Patients with FSH resistance, fertility preservation or egg donation were excluded. Participants/materials, setting, methods Only patients with AMH >2.27 ng/ml were included. Oocytes retrieved in minimally stimulated non-hCG triggered IVM cycles were matured in a monophasic IVM system. Embryos were vitrified at cleavage stage and transferred in a hormonally substituted (HRT) cycle. Baseline patient characteristics, endocrinology and embryological data were analyzed. Intra-patient analysis was done using all ART cycles (failed IVM, IVM and cART) performed in one patient. Main results and the role of chance Inter-patient analysis revealed similar age, BMI and free testosterone, whereas AMH was lower in patients with a failed cycle (8.8 ± 3.5 vs 10.9 ± 6.4 ng/mL, p = 0.03). As expected, maturation, fertilization and useable embryos differed significantly in failed vs successful cycles: respectively 31% vs 48%; 40% vs 65%; 0% vs 50%; p < 0.0001. Out of 53 patients with a failed IVM cycle, 6 had oocyte maturation problems, 11 had failed fertilization and 36 had impaired embryological development. Intra-patient analysis revealed that in the failed oocyte maturation group, 2/6 patients had maturation problems that persisted in cART cycles, indicating oocyte dysfunction. Similarly, recurrent fertilization failure was noted in 3/11 patients, due to insufficient sperm quality (n = 2). In 8/36 patients, insufficient embryo quality was observed both after IVM and cART. Hence 13/53 (24.5%) failed IVM cycles were attributed to intrinsic patient characteristics. A subgroup of patients with a failed IVM cycle had normal maturation (3/6), fertilization (7/11) or good embryos (18/36) in other IVM or cART cycles. Factors associated with cycle failure included technical issues during egg retrieval resulting in unanticipated low oocyte yield (n = 14/40), and suboptimal inclusion criteria (no PCOS, n = 3/40). Limitations, reasons for caution This was a retrospective study and holds the possibility of unmeasured confounding factors. Wider implications of the findings Risk factors for IVM failure should be identified (e.g. non-PCOS, poor operator experience) and any underlying intrinsic patient conditions should be managed within a multi-disciplinary team. Optimal patient selection is key. Analysis of failed cycles helps clinicians to estimate the prognosis of future ART cycles in women with elevated AMH. Trial registration number not applicable