Women Undergoing Fertility Treatment Research Articles

Anxiety, depression, and body image among infertile women with and without polycystic ovary syndrome.

In women undergoing fertility treatment, do those with polycystic ovary syndrome (PCOS) have a higher prevalence of symptoms of anxiety and depression and lower body appreciation than women without PCOS? Having PCOS was not associated with symptoms of anxiety and depression but was associated with somewhat lower body appreciation. PCOS has been associated with a higher chance to develop mental health problems, like anxiety, and body image concerns. The International Guidelines on PCOS recommend that all women with PCOS should routinely be screened for anxiety and depressive disorders. In most studies in this field, the comparison group included healthy women without fertility problems. We conducted a cross-sectional survey study between May 2021 and July 2023, using an online questionnaire. We informed women about this study at fertility clinics in the Netherlands through posters and leaflets and on the websites of the Dutch patient organizations Freya and Stichting PCOS. This study included women with infertility, with and without PCOS, who were undergoing fertility treatment. Women completed two assessment tools: the Hospital Anxiety and Depression Scale (HADS) and the Body Appreciation Scale-2 (BAS-2). Primary outcomes were clinically relevant symptoms of anxiety (score ≥ 11) and depression (score ≥ 11), and BAS-2 scores. Secondary outcomes were mean anxiety and depression scores and anxiety and depression scores of 8 and higher. Dichotomous outcomes and continuous outcomes were analysed using logistic and linear regression analyses adjusted for age, BMI, and duration of infertility. A total of 1025 women currently undergoing infertility treatment participated, of whom 502 (49.0%) had PCOS and 523 (51.0%) had other infertility diagnoses. We found self-reported clinically relevant symptoms of anxiety in 33.1% of women with PCOS and in 31.0% of women with other infertility diagnoses (adjusted OR: 0.99, 95% CI 0.74-1.31). Clinically relevant symptoms of depression were reported in 15.5% of women with PCOS versus 14.5% of women with other infertility diagnoses (adjusted OR: 1.04, 95% CI 0.71-1.50). Women with PCOS reported slightly less body appreciation (adjusted mean difference: -1.34, 95% CI -2.32 to -0.36). Results are based on self-report and may have been affected by sampling bias. Although guidelines recommend screening women with PCOS, feelings of anxiety and depression can be present in any woman undergoing fertility treatments. We advise fertility clinics to be aware of women's mental health issues and to offer support accordingly, as a part of routine care. This study did not receive specific funding. All authors report no conflict of interest related to the current research. This study was pre-registered at OSF: https://osf.io/qbeav.

The intrafollicular concentrations of biologically active cortisol in women rise abruptly shortly before ovulation and follicular rupture.

What is the temporal activity and the concentration in follicular fluid (FF) of the anti-inflammatory steroid cortisol during the ovulatory process in humans? Intrafollicular concentrations of cortisol become massively upregulated close to ovulation concomitant with an exceptionally high biological activity securing a timely and efficient termination of inflammatory processes. Ovulation has been described as a local, controlled inflammatory process resulting in the degeneration of the follicle wall which facilitate oocyte extrusion. Ovulation also affects the glucocorticoid metabolism of granulosa cells (GCs) and although de novo synthesis of cortisol only occurs in the adrenal cortex, the mid-cycle surge has been shown to induce a change from high expression of HSD11B2, inactivating cortisol to cortisone, to high expression of HSD11B1 which reversibly catalyses cortisol production from cortisone. Furthermore, high concentrations of progesterone and 17OH-progesterone within follicles may cause dislodging of cortisol from cortisol binding protein (CBP) thereby activating the biological activity of cortisol. This prospective cohort study included 50 women undergoing fertility treatment according to a standard antagonist protocol at a university hospital-affiliated fertility clinic in Denmark. Women donated FF and GCs from one follicle for research purpose aspirated at one of four time points during the process of final maturation of follicles: T = 0 h, T = 12 h, T = 17 h, T = 32 h. A second sample was collected at oocyte pick up at T = 36 h. The concentration of cortisol and cortisone together with a range of sex steroids was measured by LC-MS/MS in FF collected at the five time points mentioned above. Whole genome microarray data, validated by q-PCR analysis, was used to evaluate gene expression of CYP11B1, CYP21A2, HSD11B1, HSD11B2, and NR3C1 in GCs at the same time points. The concentration of cortisol was significantly increased from a few nM at 0 h to around 100-140 nM (P ≤ 0.0001) at 32-36 h, whilst cortisone was almost constant from 0 to 17 h at a concentration of between 90 and 100 nM being significantly reduced to 25-40 nM (P ≤ 0.0001) at 32-36 h. This was paralleled by a 690-fold upregulation of HSD11B1 from 0 to 12 h increasing to a more than 20.000-fold change at 36 h. HSD11B2 was quickly downregulated 15- to 20-fold after ovulation induction. Concentrations of progesterone and 17OH-progesterone increased during the ovulatory process to high levels which in essence displaces cortisol from its binding protein CBP due to similar binding affinities. Furthermore, a significant decrease in 11-deoxycortisol expression was seen, but CYP11B1 expression was below detection limit in GCs. The study included women undergoing ovarian stimulation and results may differ from the natural cycle. More observations at each specific time point may have strengthened the conclusions. Furthermore, we have not been able to measure the actual active biological concentration of cortisol. For the first time, this study collectively evaluated the temporal pattern of cortisol and cortisone concentrations during human ovulation, rendering a physiological framework for understanding potential dysregulations in the inflammatory reaction of ovulation. This research was supported by the University Hospital of Copenhagen, Rigshospitalet, and Novo Nordisk Foundation grant number NNF21OC00700556. Interreg V ÔKS through ReproUnion (www.reprounion.eu); Region Zealand Research Foundation. The funders had no role in study design, collection of data, analyses, writing of the article, or the decision to submit it for publication. The authors have no conflicts of interest to declare. N/A.

Utility of Repeat Uterine Cavity Evaluation in the Infertility Workup.

Background: Uterine cavity abnormalities contribute to infertility. The purpose of this study was to evaluate the incidence, recurrence rates, and risk factors for uterine cavity abnormalities in women undergoing infertility workup and treatment, focusing on the utility of routinely repeated imaging. Methods: Retrospective cohort study at single academic medical center of 833 infertile women who had uterine cavity evaluations performed at least 9 months apart. Results: Of 833 eligible patients, 664 (79.7%) had normal initial imaging and 169 (20.3%) had abnormal initial imaging. Among the former, 10% had abnormal uterine cavity on repeat saline infusion sonohysterography (SIS); among the latter, 32% had abnormal repeat SIS [Chi-square p < 0.0001, risk ratio 2.30 (95% confidence interval 1.85-2.86)]. On average, 23.1 ± 13.6 months passed between studies. Regardless of initial imaging findings, women with abnormal repeat SIS were older than those with normal repeat SIS, with no difference in time elapsed between studies. There were no associations between repeat imaging outcomes and body mass index, uterine instrumentation, number of treatment cycles, or maximum peak estradiol levels in a single cycle between studies. There was no difference in live birth rate among cycles started within 1 year after repeat SIS across groups. Conclusions: Uterine cavity abnormalities were found in 10% of patients on repeat imaging despite initially normal testing. No risk factors for cavity abnormality on repeat imaging were identified besides age and prior abnormality. It would be prudent to continue performing routine repeat uterine cavity evaluation for women undergoing fertility treatment, particularly if corrective measures had been taken in the past.

Perceived stress reduction through an infertility coaching program: a randomized controlled clinical trial

Infertility has been recognized as a distressing experience among couples worldwide, cutting across various cultures. This present study was conducted to assess the impact of a supportive stress management program led by an infertility coach for women undergoing fertility treatment. This randomized controlled clinical trial study was performed on 60 infertile women undergoing assisted reproductive techniques at Maryam Infertility Center located in Sari in 2018. After random allocation in two groups, 30 individuals were in the intervention group and 30 in the control group. The intervention program was implemented according to the infertility coach's counseling protocol in six stages. The control group received only routine ward counseling. In order to measure stress, the Newton Infertility Stress Questionnaire was used firstly before intervention and then after oocyte puncture, embryo transfer, and pregnancy testing. Data analysis was performed using SPSS statistical software version 18 and Shapiro–Wilk, Chi-square, Mann–Whitney, independent t-test, Friedman test, Wilcoxon test, GEE test, and Cohen's effect size. Our analysis approach has also been based on the analysis of (ITT). The significance level was 0.05. The mean ± SD scores of infertility perceived stress before the intervention in the control was 146.16 ± 16.90 and the intervention group was 156.53 ± 9.31, after intervention at the time of oocyte puncture in the controls was 165.36 ± 8.98 and the intervention group was 155.83 ± 10.70, at the day of embryo transfer in the control group was 156.35 ± 14.45 and in the intervention group was 123.58 ± 22.9 and in the pregnancy test day in the control group was 185.76 ± 26.56 and in the intervention group was 127.61 ± 21.57 (P < 0.001). According to Friedman test, the mean of stress in three situations after the intervention showed a significant difference in reduction of the mean of stress (P < 0.001). In the control group, the stress score of the samples had an increasing trend, which was significant during the measurement steps based on Friedman test results (P < 0.001). In the intervention group, paired t-test results showed no significant comparing mean score of Newton's infertility stress before and after oocyte puncture day (P = 0.711), comparing the mean of stress before and after pregnancy test day (P = 0.003) and also comparing of mean stress before and after pregnancy on the day of embryo transfer according to Wilcoxon test (P < 0.001). And comparing mean stress before and after pregnancy test day, paired t-test (P = 0.001) showed significant statistical differences. According to the results of the GEE test, changes in stress scores over time were significant between the two groups (P < 0.001), as well as the effect of stress on oocyte puncture day (0.41), embryo transfer day (1.69), pregnancy test day (P < 0.001) (2.46) had a significant effect on the day of embryo transfer and pregnancy test day. Based on the results of this study, the infertility coach program demonstrated the ability to decrease the perceived stress related to infertility. Additionally, it showed potential in enhancing treatment outcomes, such as oocyte count and positive pregnancy results, among infertile women undergoing assisted reproductive techniques.Trial registration: Iranian Registry for Clinical Trial (the link to trial: https://www.irct.ir/trial/33357). Registered 11-11-2018.

Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment

BackgroundConcerns have been raised whether exposure to endocrine-disrupting chemicals (EDCs) can alter reproductive functions and play a role in the aetiology of infertility in women. With increasing evidence of adverse effects, information on factors associated with exposure is necessary to form firm recommendations aiming at reducing exposure.ObjectiveOur aim was to identify associations between lifestyle factors including the home environment, use of personal care products (PCP), and dietary habits and concentrations of EDCs in ovarian follicular fluid.MethodsApril-June 2016, 185 women undergoing ovum pick-up for in vitro fertilisation in Sweden were recruited. Correlation analyses were performed between self-reported lifestyle factors and concentration of EDCs analysed in follicular fluid. Habits related to cleaning, PCPs, and diet were assessed together with concentration of six per- and polyfluoroalkyl substances (PFASs) [PFHxS, PFOA, PFOS, PFNA, PFDA and PFUnDA], methyl paraben and eight phthalate metabolites [MECPP, MEHPP, MEOHP, MEHP, cxMinCH, cxMiNP, ohMiNP, MEP, MOHiBP]. Spearman’s partial correlations were adjusted for age, parity and BMI.ResultsSignificant associations were discovered between multiple lifestyle factors and concentrations of EDCs in ovarian follicular fluid. After correcting p values for multiple testing, frequent use of perfume was associated with MEP (correlation ρ = 0.41 (confidence interval 0.21–0.47), p < 0.001); hens’ egg consumption was positively associated with PFOS (ρ = 0.30 (0.15–0.43), p = 0.007) and PFUnDA (ρ = 0.27 (0.12–0.40), p = 0.036). White fish consumption was positively associated with PFUnDA (ρ = 0.34 (0.20–0.47), p < 0.001) and PFDA (ρ = 0.27 (0.13–0.41), p = 0.028). More correlations were discovered when considering the raw uncorrected p values. Altogether, our results suggest that multiple lifestyle variables affect chemical contamination of follicular fluid.Impact statementThis study shows how lifestyle factors correlate with the level of contamination in the ovary by both persistent and semi-persistent chemicals in women of reproductive age. Subsequently, these data can be used to form recommendations regarding lifestyle to mitigate possible negative health outcomes and fertility problems associated with chemical exposure, and to inform chemical policy decision making. Our study can also help form the basis for the design of larger observational and intervention studies to examine possible effects of lifestyle changes on exposure levels, and to unravel the complex interactions between biological factors, lifestyle and chemical exposures in more detail.

O-057 Prevalence of T-shaped uterus among women undergoing fertility treatments based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria.

Abstract Study question What is the prevalence of a T-shaped uterus among women undergoing fertility treatments based on ESHRE/ESGE (Grimbizis et al.,2013) and CUME (Ludwin et al.,2020)? Summary answer The prevalence of T-shaped uterus was 4.1% according to the ESHRE/ESGE, and according to the CUME, 1.1% T-shaped uterus and 0.9% borderline T-shaped uterus. What is known already The definition of a T-shaped uterus by the ESHRE/ESGE consensus (Grimbizis et al., 2013) was based on three-dimensional ultrasound (3D-US) images, defining it as a narrow uterine cavity caused by thickened lateral walls with a ratio of two-thirds uterine body and one-third cervix. This definition is subjective and therefore makes giving an objective diagnosis difficult. The CUME group (Ludwin et al., 2020) described practical diagnostic criteria for a T-shaped uterus according to 3D-US images. As there is no consensus regarding the definition, the overall prevalence according to different studies varied from 0.2 to 10.0%. Study design, size, duration A retrospective cohort study with prospective analysis of 3D-US images was conducted. All women who were admitted to our unit for fertility treatments and underwent 3D-US between 12/2017-12/2021 were included. Women were grouped according to infertility type. All 3D-US images of uteri suspected to be T-shaped according to ESHRE/ESGE were assessed according to the CUME criteria, based on the following three measurements: lateral indentation angle ≤130°, lateral indentation depth ≥7 mm, and T-angle ≤40°. Participants/materials, setting, methods The study was conducted in a single university-affiliated hospital. Women who underwent fertility treatments due to various indications were included. The exclusion criteria were women undergoing fertility preservation, egg donation and oocyte recipients. All 3D-US were performed by well-trained ultrasound technicians. We first screened all images and calculated the prevalence of T-shaped uteri in our population based on the ESHRE/ESGE consensus. Next, we performed the three measurements according to the CUME criteria. Main results and the role of chance Altogether 451 women were admitted to our fertility unit. Nine cases were excluded due to unsatisfactory 3D-US images because of technical difficulties. Finally, 442 women were included in the study and divided into in the following groups: anovulation 10.6% (n = 47), mechanical factor 11.1% (n = 49), male factor 38.7% (n = 171), and unexplained infertility 39.6% (n = 175). The prevalence of T-shaped uterus according to the ESHRE/ESGE was 4.1% (n = 18). Among them, 3.2% (n = 3) were from the female factor groups (anovulation + mechanical), 4.1% (n = 7) from the male factor group, and 4.6% (n = 8) from the unexplained infertility group. Afterwards, the 3D-US images were analyzed according to the CUME criteria. T-shaped uterus was defined when all three criteria were met, and borderline T-shaped uterus was defined when two out of three criteria were met. According to CUME criteria, the prevalence of T-shaped uterus was only 1.1% (n = 5), three being from the male factor group and two from the unexplained infertility group. No T-shaped uteri were found in the female factor groups. Additionally, 0.9% (n = 4) were considered borderline T-shaped. Limitations, reasons for caution The ESHRE/ESGE consensus is subjective and may lead to either under- or over-diagnosis. On the other hand, the CUME criteria are objective and well-defined, but due to their strictness, dysmorphic uteri with very narrow uterine cavities and thickened lateral walls may not be diagnosed as T-shaped uteri. Wider implications of the findings Diagnosis and management of women with T-shaped uteri are very controversial topics. Therefore, making the diagnosis more precise and objective can help us to screen for the most significant cases and tailor the management accordingly. The similar prevalence among different infertility groups reflects the incidental nature of this diagnosis. Trial registration number Not applicable.

O-247 The intrafollicular inflammatory response during ovulation in women is most likely controlled by high concentrations of active cortisol being synthesized shortly before follicular rupture

Abstract Study question How is the anti-inflammatory response in human follicles controlled during the ovulatory process leading to the expulsion of the oocyte? Summary answer Intrafollicular concentrations of cortisol becomes high close to ovulation concomitant with an exceptionally high biological activity securing a timely and efficient termination of inflammatory processes. What is known already Ovulation has been described as a local controlled inflammatory process resulting in the degeneration of the follicle wall to facilitate oocyte extrusion. Ovulation also affects glucocorticoid metabolism of granulosa cells (GC) and although de novo synthesis of cortisol only occurs in the adrenal cortex the mid-cycle surge induces a change from high expression of HSD11b2, inactivating cortisol to cortisone, to high expression of HSD11b1 which reversibly catalyses cortisol production from cortisone. Furthermore, the high concentrations of progesterone and 17-OH-progesterone within follicles cause dislodging of cortisol from cortisol binding protein (CBP) thereby activating the biological activity of cortisol. Study design, size, duration This prospective study included 50 women undergoing fertility treatment according to a standard antagonist protocol at the fertility clinic at the university hospital of Koege, Denmark. Women donated one follicle for research purpose aspirated at one of four time points during the process of final maturation of follicles; T = 0h, T = 12h; T = 17h; T = 32h and then one additional follicle at OPU at T = 36h Participants/materials, setting, methods The concentration of cortisol and cortisone together with sex steroids were measured by LC-MS/MS in follicular fluid (FF) collected at the above five time points. Whole genome microarray data, validated by q-PCT analysis, was used to evaluate gene expression of CYP11b1, CYP21A2, HSD11b1, HSD11b2 and NR3C1 in GC at the five different time points. Main results and the role of chance The expression of HSD11b1 is strongly upregulated during the ovulatory process. From 0-12h expression is increased 690 times reaching more than 20.000 times higher than at T = 0 during the remaining period. In contrast, expression of HSD11b2 is quickly downregulated by 15-20 times through the ovulatory process. The concentration of cortisol is different from the gene expression but increases significantly from a few ng/ml at T = 0h to around 15 ng/ml at T = 12h—17h and peaks at 40-50 ng/ml at T = 32h—36h. In contrast, cortisone is almost constant from 0 to 17h at a concentration of 30-40 ng/ml being significantly reduced to 10-20 ng/ml at T = 32—36h. Concentrations of progesterone and 17-OH-progesterone increased during the ovulatory process to high levels which in essence displaces cortisol from its binding protein CPB, due to similar binding affinities. This will contribute to high levels of biologically active cortisol close to ovulation, which allows the inflammatory reaction to act on the follicle wall and secure extrusion of the oocyte to oviduct before becoming inhibited by cortisol. Furthermore, a significant decrease in 11-deoxycortisol expression was seen but CYP11B1 expression was below detection limit in GCs. This study provides new information on human ovulation. Limitations, reasons for caution Although 50 women were included more observations at each specific time point would have strengthened the conclusions. Wider implications of the findings For the first time, this study collectively evaluates the temporal effect of cortisol and cortisone concentrations in connection with gene expression profiles of enzymes involved in regulation the inflammatory response during human ovulation which now forms a physiological framework for understanding potential dysregulations in the involved processes. Trial registration number NA

Anxiety and depression in women with asthma prior to fertility treatment

ABSTRACT Objective We investigate symptoms of anxiety and depression among women with asthma prior to fertility treatment. Methods This is a cross-sectional study of women screened for eligibility to the PRO-ART study (RCT of omalizumab versus placebo in asthmatic women undergoing fertility treatment (NCT03727971)). All participants were scheduled for in vitro fertilization (IVF) treatment at four public fertility clinics in Denmark. Data on demographics and asthma control (ACQ-5) were obtained. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS-A and D, respectively) and defined as being present on both subscales if a score >7 was obtained. Spirometry, diagnostic asthma test, and measurement of fractional exhaled nitric oxide (FeNO) were conducted. Results A total of 109 women with asthma were included (mean age 31.8 ± 4.6 and BMI 25.5 ± 4.6). Most women had male factor infertility (36.4%) or unexplained infertility (35.5%). Twenty-two percent of the patients reported uncontrolled asthma (ACQ-5 score > 1.5). The mean HADS-A and HADS-D scores were 6.0 ± 3.8 (95% CI 5.3–6.7) and 2.5 ± 2.2 (95% CI 2.1–3.0), respectively. Thirty (28.0%) women reported anxiety symptoms, and four (3.7%) had concomitant depressive symptoms. Uncontrolled asthma was significantly associated with both depressive (p = 0.04) and anxiety symptoms (p = 0.03). Conclusions More than 25% of women with asthma prior to fertility treatment had self-reported symptoms of anxiety, and just below 5% had self-reported depressive symptoms, possibly related to uncontrolled asthma.

(177) Female Sexual Dysfunction: Can it be Addressed During Infertility Treatment?

Abstract Introduction Female sexual dysfunction (FSD) is a highly prevalent and distressing condition in the general population. Women undergoing fertility treatments are at even higher risk of developing sexual dysfunction due to sexual activity being perceived as an obligation to conceive versus for pleasure, stress of whether the current act of intercourse will result in conception, and a sense of sexual activity as being part of a demanding medical treatment regimen. Objective The purpose of this review is to investigate currently used interventions and/or treatments of FSD in the settings of infertility treatment. Methods We conducted a systematic review on the current approaches to treat FSD while undergoing fertility treatments. PubMed, PMC and Google Scholar were queried, and results were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria for this review were female subjects undergoing infertility treatment, sexual health was described and measured, interventions were performed or recommended to the subjects with measured outcomes, and the manuscript was written in English between January 2000 to June 2022. Case reports and studies that did not address conditions of interest were excluded from analysis. Results Queries identified 2,341 studies of which title and summary were screened. Fourteen articles met inclusion criteria and underwent full text review. Although multiple studies described an association between infertility and different types of FSD, no study described outcomes for FSD interventions in the infertility setting. Conclusions There is a complete lack of FSD treatment options for infertility patients. Clinicians treating infertility patients should consider discussing FSD and its treatment options in this population. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Abbvie, Coloplast, Sprout Pharmaceuticals.

Perfluorohexane sulfonate (PFHxS) disturbs the estrous cycle, ovulation rate, oocyte cell communication and calcium homeostasis in mice

Perfluoroalkyl substances are man-made chemicals with ample consumer and industrial applications. They are widely used and are resistant to environmental and metabolic degradation. Several studies have evaluated the effects of Perfluorohexane sulfonate on reproduction. However, there are few reports exploring the cell and molecular mechanisms of its toxicity in the ovary. The aim of this study was to investigate the effects of PFHxS exposure on the estrous cycle, ovulation rate, and the underlying mechanisms of action in female mice in vivo. The animals received a single sub-lethal dose of PFHxS (25.1 mg/kg, 62.5 mg/kg) or vehicle and were stimulated to obtain immature cumulus cell-oocyte complexes (COCs) from the ovaries, or superovulated to develop mature COCs. To evaluate oocyte physiology, Gap-junction intercellular communication (GJIC) was analyzed in immature COCs and calcium homeostasis was evaluated in mature oocytes. PFHxS exposure prolonged the estrous cycle and decreased ovulation rate in female mice. Connexins, Cx43 and Cx37, were downregulated and GJIC was impaired in immature COCs, providing a possible mechanism for the alterations in the estrous cycle and ovulation. No morphological abnormalities were observed in the mature PFHxS-exposed oocytes, but calcium homeostasis was affected. This effect is probably due, at least partially, to deregulation of the endoplasmic reticulum calcium modulator, Stim1. These mechanisms of ovarian injury could explain the reported correlation among PFHxS levels and subfertility in women undergoing fertility treatments.

(121) Female Sexual Dysfunction: Can it be Addressed During Infertility Treatment?

Abstract Introduction Female sexual dysfunction (FSD) is a highly prevalent and distressing condition in the general population. Women undergoing fertility treatments are at higher risk of developing sexual dysfunction due to associated stress, sense of sexual activity as being routine, and demanding treatment regimens. Despite the known association between FSD and infertility, the optimal FSD treatment regimen for the infertility patient has not been described. Objective Our objective was to determine the optimal FSD treatment strategy for women with infertility. Methods We conducted a systematic review on the current approaches to treat FSD while undergoing fertility treatments. PubMed, PMC and Google Scholar were queried, and results were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria for this review were: 1) Subjects were women presenting for infertility treatment, 2) Sexual health was described and measured, 3) Interventions were performed or recommended to the subjects with measured outcomes and 4) The manuscript was written in English between January 2000 to June 2022. Case reports and studies that did not address conditions of interest were excluded from analysis. Results Queries identified 2,341 studies of which title and summary were screened. 15 articles were identified for full text review, and only 1 article met inclusion criteria. The single article identified was a prospective cohort study including 35 women with infertility in each arm. The intervention arm underwent 2 sessions of sexual counseling following the BETTER method, and at a 3 month follow up period FSFI scores were significantly improved in the intervention arm compared to the control arm. Conclusions Given the significant risk for FSD in this population, the fact that only one study could be identified on this topic is a huge gap in the medical knowledge that requires more investigation. The single study identified suggests counseling may be a successful treatment option for women with FSD and infertility, but more studies are needed to determine what other options are available and effective for FSD in this population. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Ferrring pharmaceuticals

Factors affecting the distribution of serum anti-müllerian hormone levels among infertile Asian women: a multi-nation, multi-centre, and multi-ethnicity prospective cohort study.

How do age, ethnicity, and other characteristics affect serum anti-mullerian hormone (AMH) levels in Asian women undergoing fertility treatment? Age, ethnicity, obesity (BMI ≥ 30 kg/m2), and polycystic ovarian syndrome (PCOS) significantly impacted serum AMH levels, with the rate of decrease accelerating as age increased; a concentration of 4.0 ng/ml was the optimal cut-off for diagnosis of PCOS. There are significant differences in ovarian reserve among women from different races and ethnicities, and Asian women often have poorer reproductive outcomes during assisted reproductive treatment cycles. A population-based multi-nation, multi-centre, multi-ethnicity prospective cohort study of 4613 women was conducted from January 2020 to May 2021. Infertile women of 20-43 years of age were enrolled. The exclusion criteria included: age <20 or >43, non-Asian ethnicity, and missing critical data. Participants were Asian women of Chinese, Japanese, Korean, Thai, Vietnamese, Malay, Indian, and Indonesian ethnicities from 12 IVF centres across Asia. These women were all naïve to ovarian stimulation cycles and attended IVF centres for fertility assessment. The AMH measurement was performed using an AMH automated assay on a clinically validated platform. A total of 4556 infertile Asian women were included in the final analyses. The mean ± SD for serum AMH concentrations (ng/ml) across specific age groups were: overall, 3.44 ± 2.93; age <30, 4.58 ± 3.16; 30-31, 4.23 ± 3.23; 32-33, 3.90 ± 3.06; 34-35, 3.21 ± 2.65; 36-37, 2.74 ± 2.44; 38-39, 2.30 ± 1.91; 40 and above, 1.67 ± 2.00. The rate of AMH decrease was ∼0.13 ng/ml/year in patients aged 25-33 and 0.31 ng/ml/year in women aged 33-43. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%). Age (P < 0.001), ethnicity (P < 0.001), obesity (P = 0.007), PCOS (P < 0.001), and a history of endometrioma cystectomy (P = 0.01) were significantly associated with serum AMH values. Smoking status, pretreatment with GnRH agonist (GnRHa) or the oral contraceptive pill (OCP), freezing-thawing of blood samples, and sampling on Day 2 to Day 5 of the menstrual cycle or randomly did not appear to affect serum AMH levels. An AMH concentration of 4.0 ng/ml was the optimal cut-off for PCOS diagnosis with a sensitivity of 71.7% and specificity of 75.8% (AUC = 0.81, CI 95%: 0.79-0.83; P < 0.001). The incidence of PCOS was supposedly high in this cohort as some IVF clinics were tertiary referral centres for managing specific fertility issues encountered by women with PCOS. Treatment with GnRHa or OCP before AMH testing was regionally and ethnically confined, mostly in Hong Kong SAR and Japan. Moreover, this reference for serum AMH value is limited to Asian women of the ethnicities examined and may not apply to other ethnicities not included in the study. This is the first study to collate and construct age-specific reference ranges for serum AMH levels using the same bioassay on Asian women of different ethnicities. The findings of this investigation can assist clinicians to counsel and prognosticate about Asian women's ovarian reserve and reproductive potential, thus providing better strategies for personalized fertility interventions. This study was technically supported by Ferring Pharmaceuticals and received no specific grant from any funding agency. All authors have no competing interests to disclose. NCT04203355.

Sexual attraction to visual sexual stimuli in association with steroid hormones across menstrual cycles and fertility treatment

BackgroundSteroid hormones (i.e., estradiol, progesterone, and testosterone) are considered to play a crucial role in the regulation of women’s sexual desire and sexual attraction to sexual stimuli throughout the menstrual cycle. However, the literature is inconsistent, and methodologically sound studies on the relationship between steroid hormones and women’s sexual attraction are rare. MethodsThis prospective longitudinal multisite study examined estradiol, progesterone, and testosterone serum levels in association with sexual attraction to visual sexual stimuli in naturally cycling women and in women undergoing fertility treatment (in vitro fertilization, IVF). Across ovarian stimulation of fertility treatment, estradiol reaches supraphysiological levels, while other ovarian hormones remain nearly stable. Ovarian stimulation hence offers a unique quasi-experimental model to study concentration-dependent effects of estradiol. Hormonal parameters and sexual attraction to visual sexual stimuli assessed with computerized visual analogue scales were collected at four time points per cycle, i.e., during the menstrual, preovulatory, mid-luteal, and premenstrual phases, across two consecutive menstrual cycles (n = 88 and n = 68 for the first and second cycle, respectively). Women undergoing fertility treatment (n = 44) were assessed twice, at the beginning and at the end of ovarian stimulation. Sexually explicit photographs served as visual sexual stimuli. ResultsIn naturally cycling women, sexual attraction to visual sexual stimuli did not vary consistently across two consecutive menstrual cycles. While in the first menstrual cycle sexual attraction to male bodies, couples kissing, and at intercourse varied significantly with a peak in the preovulatory phase, (all p ≤ 0.001), there was no significant variability across the second cycle. Univariable and multivariable models evaluating repeated cross-sectional relationships and intraindividual change scores revealed no consistent associations between estradiol, progesterone, and testosterone and sexual attraction to visual sexual stimuli throughout both menstrual cycles. Also, no significant association with any hormone was found when the data from both menstrual cycles were combined. In women undergoing ovarian stimulation of IVF, sexual attraction to visual sexual stimuli did not vary over time and was not associated with estradiol levels despite intraindividual changes in estradiol levels from 122.0 to 11,746.0 pmol/l with a mean (SD) of 3553.9 (2472.4) pmol/l. ConclusionsThese results imply that neither physiological levels of estradiol, progesterone, and testosterone in naturally cycling women nor supraphysiological levels of estradiol due to ovarian stimulation exert any relevant effect on women’s sexual attraction to visual sexual stimuli.

Regulation of human oocyte maturation in vivo during the final maturation of follicles.

Which substances and signal transduction pathways are potentially active downstream to the effect of FSH and LH in the regulation of human oocyte maturation in vivo? The regulation of human oocyte maturation appears to be a multifactorial process in which several different signal transduction pathways are active. Many studies in animal species have provided insight into the mechanisms that govern the final maturation of oocytes. Currently, these studies have identified several different mechanisms downstream to the effects of FSH and LH. Some of the identified mechanisms include the regulation of cAMP/cGMP levels in oocytes involving C-type natriuretic peptide (CNP), effects of epidermal growth factor (EGF)-related peptides such as amphiregulin (AREG) and/or epiregulin (EREG), effect of TGF-β family members including growth differentiation factor 9 (GDF9) and morphogenetic protein 15 (BMP15), activins/inhibins, follicular fluid meiosis activating sterol (FF-MAS), the growth factor midkine (MDK), and several others. However, to what extent these pathways and mechanisms are active in humans in vivo is unknown. This prospective cohort study included 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital affiliated fertility clinic in 2016-2018. We evaluated the substances and signalling pathways potentially affecting human oocyte maturation in follicular fluid (FF) and granulosa cells (GCs) collected at five time points during the final maturation of follicles. Using ELISA measurement and proteomic profiling of FF and whole genome gene expression in GC, the following substances and their signal transduction pathways were collectively evaluated: CNP, the EGF family, inhibin-A, inhibin-B, activins, FF-MAS, MDK, GDF9, and BMP15. All the evaluated substances and signal transduction pathways are potentially active in the regulation of human oocyte maturation in vivo except for GDF9/BMP15 signalling. In particular, AREG, inhibins, and MDK were significantly upregulated during the first 12-17 h after initiating the final maturation of follicles and were measured at significantly higher concentrations than previously reported. Additionally, the genes regulating FF-MAS synthesis and metabolism were significantly controlled in favour of accumulation during the first 12-17 h. In contrast, concentrations of CNP were low and did not change during the process of final maturation of follicles, and concentrations of GDF9 and BMP15 were much lower than reported in small antral follicles, suggesting a less pronounced influence from these substances. None. Although GC and cumulus cells have many similar features, it is a limitation of the current study that information for the corresponding cumulus cells is not available. However, we seldom recovered a cumulus-oocyte complex during the follicle aspiration from 0 to 32 h. Delineating the mechanisms governing the regulation of human oocyte maturation in vivo advances the possibility of developing a platform for IVM that, as for most other mammalian species, results in healthy offspring with good efficacy. Mimicking the intrafollicular conditions during oocyte maturation in vivo in small culture droplets during IVM may enhance oocyte nuclear and cytoplasmic maturation. The primary outlook for such a method is, in the context of fertility preservation, to augment the chances of achieving biological children after a cancer treatment by subjecting oocytes from small antral follicles to IVM. Provided that aspiration of oocytes from small antral follicles in vivo can be developed with good efficacy, IVM may be applied to infertile patients on a larger scale and can provide a cheap alternative to conventional IVF treatment with ovarian stimulation. Successful IVM has the potential to change current established techniques for infertility treatment. This research was supported by the University Hospital of Copenhagen, Rigshospitalet, the Independent Research Fund Denmark (grant number 0134-00448), and the Interregional EU-sponsored ReproUnion network. There are no conflicts of interest to be declared.

Personal Growth and Life Satisfaction during Fertility Treatment-A Comparison between Arab and Jewish Women.

Coping with difficulty conceiving and the ensuing fertility treatments is a stressful experience that impacts many aspects of women's lives. On the basis of Lazarus and Folkman's model of stress and coping and Schaefer and Moos's model of personal growth, and in view of the sparse literature on cultural aspects of infertility and personal growth, this study examined the relationship between stress on the one hand and personal growth and life satisfaction on the other among Arab and Jewish Israeli women. Furthermore, it investigated the moderating role played by perceived stigma, coping flexibility, cultural orientation (individualism and collectivism), and ethnicity. Two hundred five Arab and Jewish Israeli women undergoing fertility treatment completed self-report questionnaires. The results show that Arab women reported higher levels of personal growth and individualism than Jewish women. In the whole sample, a linear negative relationship was found between stress and life satisfaction, and a curvilinear relationship was found between stress and personal growth. In addition, perceived stigma, collectivism, individualism, and coping flexibility were found to moderate the association between perceived stress and personal growth. The findings provide further understanding of personal growth in the context of infertility, showing that personal resources and perceptions are more important than cultural differences in this regard.

Pharmacotherapy for Infertility in Ghana: A Prospective Study on Prescription Patterns and Treatment Outcomes among Women undergoing Fertility Treatment

Pharmacotherapy remains a first-line and major treatment option for couples struggling with infertility, especially in sub-Saharan Africa, where other expensive alternatives are rarely available. Despite the reliance on pharmacotherapy for treating infertility in the subregion, especially for those diagnosed with unexplained infertility, little is known about the actual influence of drug therapies on conception. The study aimed to prospectively assess the prescription patterns and outcomes of pharmacotherapy for women undergoing fertility treatment in Ghana. This prospective cohort study involved 482 infertile women presenting for fertility treatment in 4 fertility clinics in the Cape Coast Metropolis of Ghana between March 2019 and February 2021. A simple random sampling technique was used to recruit subjects for the study. The women were followed up for 12 months to assess the outcome of drug therapy on conception. Data analysis was done using Stata version 14. Logistic regression was used to assess the association between trends with dichotomous outcomes. The study identified that approximately 45.2% of the patients received monotherapy, whereas 24.1% received a combination of 2 drugs. Patients treated with a combination of 3 drugs were more likely to conceive (adjusted odds ratio = 4.10; 95% CI, 1.29-13.02; P = 0.02) than those without treatment. Patients treated with combination therapies had higher chances of conception than those without medications. However, a combination of nutritional and herbal therapies were associated with improved outcomes compared with conventional and nutritional supplements. The study's outcome could provide fertility specialists and stakeholders insight into choosing appropriate treatment options for prospective couples seeking fertility care. Consequently, fertility patients can access specific treatment options to meet their desired needs.

Psychological Issues among Women Undergoing Fertility Treatment in a Specialist Fertility Hospital, South East Nigeria

Introduction: In Nigeria, a major reason for marriage is procreation and married couples look forward to having children within a year or two of marriage. The inability to achieve conception and subsequently have a child among couples may lead to psychological complications. Objective: This study assessed the psychological impact of infertility and its management on women receiving treatment at a Fertility Specialist Hospital in a poor resource setting. Methods: This was a cross-sectional study of 376 consenting married women who sought and received fertility treatment at a private Fertility Specialist Hospital, located at Abakaliki, South-East Nigeria between May 1, 2017 and May 31, 2022. Socio-demographic and Structured questionnaires were administered to the participants over a 5-year period. Results: The mean age of the women at presentation was 36.9 (±7.2 SD) years. The majority of the women (227) presented with secondary infertility accounting for 60.4%, while the rest had primary infertility (χ2 = 16.18, P = 0.001). Male-only factor infertility accounted for 22.9% of all the infertility cases, female-only factor 21.3% while both (male and female factors co-existing) accounted for 52.7% of all the cases. The commonest cause of infertility in the study was poor sperm parameters (176) accounting for 46.8% of cases, tubal factor 19.1% and anovulatory factor 22.3% (χ2 = 214.21, P = 0.001). Three hundred and thirty four (88.8%) felt depressed, 266 (70.7%) felt guilty about the past, and 222 (59.0%) had suicidal tendencies because of the infertility ordeal. Two hundred and fifty one (66.8%) felt inferior, 237 (63.0%) cried often and 174 (46.3%) were socially withdrawn. However, 10.4% of the women felt satisfied and well. These negative psychological feelings were statistically significant. Concerning the effect on marriage, the closeness of couples was reduced significantly in 57.7%, 62.8% had reduced coital intimacy, 79.3% had frequent quarrel and misunderstanding, 27.9% had threats of divorce while 4.5% had actually divorced and 11.% separated. However, there was no negative effect of infertility in 8.8% of couples. Conclusion: Psychological issues associated with infertility and its management in women include feelings of depression, guilt feelings, suicidal ideation, weeping episodes, social withdrawal, feelings of inferiority, reduced libido, and poverty of intimacy with frequent quarrels and misunderstanding. Women appear to bear more of the psychological issues associated with infertility. Early marriage on the part of the women, preservation of their reproductive youthful ages, and a better understanding of the concept of infertility by the couple will not only reduce the prevalence of infertility but will also reduce the dangerous psychological issues associated with infertility.

The Assisted Reproductive Technology (Regulation) Act, 2021: A Step in the Right Direction.

The Assisted Reproductive Technology (Regulation) Act, 2021, was passed on December 20, 2021 by an act of Parliament to regulate the functioning of assisted reproductive technology (ART) clinics and ART banks in the country. Since the dawn of in vitro fertilization (IVF), there has been a mushrooming of ART clinics in the country. There was need to supervise and regulate the functioning of these clinics and to safeguard the rights of women undergoing fertility treatment at these centers. The passing of this Act will go a long way in the better supervision, regulation, licensing, and smooth functioning of ART clinics and ART banks. The Act also brings into its ambit the controversial treatment of surrogacy and hence ensures protection of the rights of surrogate mothers. Moreover, strict implementation of the act will guarantee the success of the treatment within the legal and ethical framework.

A Rare Case of Shared Delusion of Pregnancy in a Couple Undergoing Fertility Treatment

Pseudocyesis or phantom pregnancy is a false belief of being pregnant that is associated with objective signs and reported symptoms of pregnancy, which may include abdominal enlargement, reduced menstrual flow, amenorrhea, subjective sensation of fetal movement, nausea, breast engorgement and secretions, and labor. Though it is a very rare condition, it is often seen in women undergoing fertility treatment in developing countries. Isolated pseudocyesis in women and sometimes men have been reported before, but there are very few reports of shared delusions of pregnancy by a couple. No such report has ever been made before from Nepal. Therefore, this case report seeks to associate psychiatric/psychological, gynecological, and neuroendocrine mechanisms leading to the emergence of shared delusion of pregnancy (folie à deux) in a Nepali couple undergoing artificial reproductive techniques for the management of infertility. In this case, the couple firmly believed in their pregnancy against all medical evidence. 

Role of pyroglutamic acid in cumulus cells of women with polycystic ovary syndrome.

Polycystic ovary syndrome is a complex heterogeneous endocrine disorder associated with established metabolic abnormalities and is a common cause of infertility in females. Glutathione metabolism in the cumulus cells (CCs) of women with PCOS may be correlated to the quality of oocytes for infertility treatment; therefore, we used a metabolomics approach to examine changes in CCs from women with PCOS and oocyte quality. Among 135 women undergoing fertility treatment in the present study, there were 43 women with PCOS and 92 without. CCs were collected from the two groups and levels of pyroglutamic acid were measured using LC-MS/MS followed by qPCR and Western blot analysis to examine genes and proteins involved in pyroglutamic acid metabolism related to glutathione synthesis. Women with PCOS showed increased levels of L-pyroglutamic acid, L-glutamate, and L-phenylalanine and decreased levels of Cys-Gly and N-acetyl-L-methionine. Gene expression of OPLAH, involved in pyroglutamic synthesis, was significantly increased in women with PCOS compared with those without. Gene expression of GSS was significantly decreased in women with PCOS and synthesis of glutathione synthetase protein was decreased. Expression of nuclear factor erythroid 2-related factor 2, involved in resistance to oxidative stress, was significantly increased in women with PCOS. CCs of women with PCOS showed high concentrations of pyroglutamic acid and reduced glutathione synthesis, which causes oxidative stress in CCs, suggesting that decreased glutathione synthesis due to high levels of pyroglutamic acid in CCs may be related to the quality of oocytes in women with PCOS.