Unexplained Infertility Group Research Articles

Comparative analysis of conventional in vitro fertilization and intracytoplasmic sperm injection in patients with polycystic ovarian syndrome, tubal factor infertility, and unexplained infertility whose partners exhibit normal semen parameters: A retrospective study of sibling oocytes.

This study compared the outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in patients with polycystic ovarian syndrome (PCOS), tubal factor (TF) infertility, and unexplained infertility whose partners had normal semen parameters. This retrospective study included 360 couples diagnosed with infertility involving PCOS (n=157), unexplained infertility (n=140), and TF infertility (n=63). Sibling oocytes were randomly assigned to undergo ICSI or conventional IVF insemination. The fertilization rate and embryo morphology were evaluated as outcomes. Retrieved cumulus-oocyte complexes from patients with PCOS (2,974), unexplained infertility (1,843), and TF infertility (844) were split and inseminated by conventional IVF and ICSI respectively. In comparison to the ICSI method, the conventional IVF approach was linked to a significantly higher fertilization rate in groups with PCOS (68.81% vs. 77.49%), unexplained infertility (67.62% vs. 78.84%), and TF issues (69.23% vs. 78.63%) (p<0.05). The proportion of embryos with grade A produced by the conventional IVF method was significantly higher than that produced using the ICSI method in the PCOS and unexplained infertility groups (p<0.05). Additionally, the percentage of grade B embryos produced with the ICSI method was significantly higher than that produced with the conventional IVF method in PCOS patients (p=0.002). Our results indicated that the conventional IVF method was associated with higher zygote production and a higher proportion of grade A embryos when all infertile groups were evaluated together. Thus, ICSI is not suggested for patients with these causes of infertility if their partner has normal semen parameters.

Evaluation of ovarian reserve in unexplained ınfertile cases: a case-controlled study

BackgroundThe aim of this study was to evaluate the effectiveness of current ovarian reserve tests in unexplained infertile cases.Material and methodsThis case–control study was conducted on 70 unexplained infertile women who were included in a tertiary university hospital. Both groups of basal FSH, estradiol, antimullerian hormone (AMH), inhibin B, ovarian volume, total antral follicle count (AFC), ovarian volume, and ovarian stromal blood flow (peak systolic velocity (PSV), S/D (systole and diastole ratio), resistance index (RI), and pulsatility index (PI)) values were compared.ResultsThe mean AMH, inhibin B, PSV, and stromal blood flow values of the control group patients were higher than those in the unexplained infertility group. However, the values of the means of RI and PI of the cases in the control group were lower than those in the infertility group. When PI’s value was ≥ 2.00, its sensitivity was 65.7%, and its specificity was 64.3%. In the case of the RI, its value was ≥ 0.745, its sensitivity was 65.7%, and its specificity was 62.9%. In order to show ovarian reserve in unexplained infertile cases, the sensitivity values can be sorted from high to low as follows: PI > RI > estradiol > FSH > ovarian volume > AFC > inhibin B > stromal blood flow > PSV > S/D.ConclusionIn the unexplained infertile patient group with normal ovarian reserve test results, basal estradiol, decreased PI, and RI values may be used as good ovarian reserve predictors.

Evaluation of vitamin E levels, antioxidant enzymes and malondialdehyde in women with unexplained infertility

Unexplained infertility is a perplexing disorder. 30% of infertile couples are diagnosed with unexplained infertility with all standard fertility investigations normal. Oxidative stress has been shown to have a negative impact on reproductive function in women with endometriosis and (PCOS) polycystic ovarian syndrome. In another study antioxidant supplementation improved OS induced infertility. Many studies have demonstrated an increase in Malondialdehyde in serum of women with infertility and vitamin E as a protective antioxidant in the body with positive effect on the fertility. There is growing evidence linking OS and unexplained infertility.Based on this knowledge the specific group of unexplained infertile women were chosen to assess their levels of serum antioxidant enzymes, Vitamin E and lipid peroxidation marker. To compare the Levels of Malondialdehyde, Antioxidant enzymes and Vitamin E in the serum of women with unexplained infertility and control group.: Case control study.70 normal ovulatory women who conceived within 12 months of contraceptive free intercourse, and with no history of miscarriage were recruited in the control group. 70 women with unexplained infertility were recruited as study group. All participants included in the study were between 28 and 38 years of age. Serum levels of MDA, Antioxidant enzymes (GST, SOD, Catalase) and Vitamin E concentrations were compared between two groups. Vitamin E concentrations were determined by using High performance liquid chromatography. Antioxidant enzymes and MDA were measured by standard spectrophotometric assay.: Data was analysed using SPSS Software. Continuous parameters were analysed using Mann Whitney U test. There is a significant decrease in the vitamin E levels 3.80 ug/ml) in the unexplained infertile group as compared to controls 6.0 ug/ml). All women in the study group showed significantly (P&amp;#60;0.05) higher levels of MDA and lower levels of antioxidant enzymes such as GST, SOD and Catalase as compared to the fertile women. This decrease was found to be significant with p value of &amp;#60;0.05. The study group have a higher oxidative stress status and low level of antioxidants compared to control group. Serial measurement of oxidative stress biomarkers and their defense system may help to understand the aetiology of unexplained infertility and to enhance their chances of conception.

The effect of chronic endometritis and treatment on patients with unexplained infertility

PurposeThis paper was mainly conducted to investigate the effect of chronic endometritis (CE) on the clinical outcome of patients with unexplained infertility.Materials and methods145 patients with unexplained infertility from the Reproductive Center of our hospital from January 2018 to December 2021 were selected as the unexplained infertility group. 42 patients with definite infertility causes were selected as the control group during the same period. Both groups of patients underwent hysteroscopy and immunohistochemical tests for CD38 and CD138. According to the results of hysteroscopy and immunohistochemistry, the incidence of CE between the two groups was analyzed. Patients with CE as CE group accepted oral antibiotic therapy for 14 days. Another 58 patients with unexplained infertility who did not undergo hysteroscopy and immunohistochemical tests for CD38 and CD138 were selected as the unexamined group. Both groups of patients were expected natural pregnancy. Follow-up lasted for 1 year, and the pregnant patients were followed up until delivery.The clinical pregnancy rate, spontaneous abortion rate and baby-carrying home rate of the two groups were compared.ResultsThere were 75 patients with CE in the unexplained infertility group, and the prevalence rate was 51.7% (75/145). Compared with the control group (28.6%), the incidence of CE was significantly higher (P < 0.05). After treated with antibiotic treatment, the patients’ clinical pregnancy rate was 61.3% (46/75) and baby-carrying home rate was 60% (45/75) in the CE group, which were higher than those in the unexamined group(43.1% & 36.2%) (P < 0.05), while the spontaneous abortion rate was 2.2% (1/46),which was lower than that in the unexamined group (16.0%) (P < 0.05).ConclusionsFor patients with unexplained infertility, hysteroscopy combined with endometrial immunohistochemical detection of CD38 and CD138 should be performed in time to exclude CE. The clinical pregnancy outcome of CE patients can be significantly improved by antibiotic treatment.

Cervical fluid pH, electrolytes and osmolarity changes and expression of ion transporters (ENaC, CFTR and AQP) in cervix of women with primary unexplained infertility.

Unexplained infertility could arise from a defect in the cervix. However, the contribution of abnormal cervical fluid microenvironment to this problem still needs to be identified. Therefore, this study identifies the changes in the cervical fluid microenvironment, i.e., pH, electrolytes and osmolarity as well as expression of ion transporters in the cervix including ENaC, CFTR and AQP in fertile women and in women suffering from primary unexplained infertility. Fertile women and women with unexplained infertility but having regular 28-day menstrual cycles were chosen in this study, Day-22 serum progesterone levels were determined. In the meantime, serum FSH and LH levels were determined on day 2 while, cervical flushing was performed at day 14 to analyse changes in the cervical fluid pH, osmolarity, Na+ and Cl- levels. Meanwhile, cells retrieved from cervical fluid were subjected to mRNA expression and protein distribution analysis for CFTR, AQP and ENaC by qPCR and immunofluorescence, respectively. No significant changes in serum progesterone, FSH and LH levels were observed between the two groups. However, cervical fluid pH, osmolarity, Na+ and Cl- levels were significantly lower in primary unexplained infertile group when compared to fertile group. Expression of CFTR and AQP (AQP 1, AQP 2, AQP 5 and AQP 7) in endocervical cells was lower and expression of β-ENaC was higher in primary unexplained infertile women (p < 0.05 when compared to fertile group). Alterations in the cervical fluid microenvironment linked to the defective ion transporter expression in the cervix might contribute towards the unfavourable condition that accounts for unexplained infertility in women.

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.

The Role of Anti-Sperm Antibodies in Primary, Secondary, Immunological and Idiopathic Infertility in Men

The current study aimed to conduct a statistical study to find out the numbers of men with primary and secondary infertility, immunological infertility and Idiopathic infertility in the city of Tikrit with an estimate of the levels of some sex hormones and physiological and immunological variables. The study included 400 married men who attended the Urology Department at Salah Al-Din Hospital and private clinics in the city of Tikrit and its environs for the period from April 2021 to February 2022, and their ages ranged from (20-50) years, and they were divided into two main groups as follows: It included (80) men, and it was divided into four sub-groups, namely: - The group of patients with primary infertility and included 20 individuals. The group of patients with secondary infertility included 20 individuals. And the group of immunocompromised patients included 20 individuals. And the group of patients with unexplained infertility included 20 individuals. The group of natural (fertile) individuals: It is the fifth group and represents the control group, which included (20) individuals. The results showed that the percentage of primary infertility was the highest among infertile patients, reaching 41%, while the percentage was lowest for immunological infertility, reaching 7%. While the percentage of secondary and unexplained infertility was 21% and 31%, respectively. On the other hand, the results showed that there were significant differences (P&lt;0.05) in sperm parameters between the study groups, as sperm concentrations and the percentage of mobile sperm showed a significant decrease (P&lt;0.05), especially in the secondary infertility group compared to the control group. As for the percentage of slow-moving sperms, there were no significant changes (P&lt;0.05) in all infertile groups compared with the control group. As for the percentage of non-motile sperms, it showed a significant increase (P&lt;0.05), especially in the unexplained infertility group compared with the control group. With regard to sperm shape, the percentage of deformed sperm showed a significant increase (P&lt;0.05), especially in the primary infertility group compared with the control group. The results of the current study also showed that there were significant differences (P &lt; 0.05) in the concentrations of hormones between the study groups, as the concentrations of testosterone showed a significant decrease (P &lt; 0.05), especially in the primary infertility group compared with the control group, while the least significant decrease was recorded (P&lt;0.05) in testosterone concentration in the unexplained infertility group. Regarding the prolactin hormone, a significant increase (P&lt;0.05) was recorded in the infertility groups compared with the control group, as it was significantly higher in the secondary infertility group. LH also showed significant differences (P&lt;0.05) between the study groups, and the highest significant increase was in the primary infertility group compared to the control group, while the unexplained infertility group did not show any significant differences compared to the control group. As for the FSH hormone, it showed significant differences (P&lt;0.05) between the study groups, as it recorded the highest significant increase in the primary infertility group compared to the control group, while the unexplained infertility group did not show any significant differences compared to the control group. The results of the current study also showed that there were significant differences (P&lt;0.05) in the concentrations of immunoglobulins between the study groups, as the concentrations of IgA showed a significant decrease (P&lt;0.05), especially in the secondary infertility group compared with the control group, while the least significant increase was recorded (P&lt;0.05). 0.05) in the concentration of IgA in the immunocompromised group. Regarding IgG, a significant increase (P&lt;0.05) was recorded in the infertile groups compared with the control group, if the highest significant increase was in the immunocompromised group. While the primary and secondary infertility group did not show any significant differences compared to the control group. IgM showed significant differences (P &lt; 0.05) between the study groups, and the highest significant increase was in the immunocompromised infertility group compared with the control group, while the primary and secondary infertility groups did not show any significant differences compared with the control group. Also, ASA concentrations showed a significant increase (P&lt;0.05), especially in the unexplained infertility group, while no significant change (P&lt;0.05) was recorded in the ASA concentration in the primary infertility group. With regard to white blood cells, the percentage of white blood cells showed a significant increase (P&lt;0.05), especially in the group of immunocompromised infertility, while the percentage of white blood cells was lowest in the group of primary infertility.

Impact of body mass index and vitamin D on serum AMH levels and antral follicle count in PCOS.

To investigate the effects of body mass index (BMI) values and 25(OH) vitamin D levels determined by Endocrine Society on serum Anti Mullerian Hormone (AMH) and antral follicle count (AFC) in women with polycystic ovary syndrome (PCOS). Sixty infertile women with PCOS and 30 age-matched women with unexplained infertility (UEI), were included. Patients in PCOS and control groups were divided into three subgroups according to their BMI values as normal, overweight and obese. Each BMI group was divided into three subgroups according to vitamin D levels. While AMH and vitamin D levels were determined at first admission, AFC was measured on the third day of cycle. BMI, AFC, and AMH levels of women with PCOS were significantly higher than the UEI group. AMH values of women with PCOS with normal BMI were found to be significantly higher than UEI controls with normal BMI. AMH values of overweight and obese PCOS patients and controls were similar. As BMI values of the PCOS group increased, vitamin D levels decreased significantly. Vitamin D levels of the patients in the PCOS group were found to be significantly lower than the control group. When evaluated according to BMI, the vitamin D levels of normal, overweight and obese women with PCOS were significantly lower than the UEI. Rising BMI in PCOS leads to a significant decrease in vitamin D and AMH. Deficiency, insufficiency or normality of vitamin D do not affect the main markers of ovarian reserve.

Evaluation of laparoscopy results for the patients with chronic pelvic pain

Aim: The study aims to retrospectively evaluate the laparoscopy results of patients who underwent laparoscopy with chronic pelvic pain (CPPS) diagnosis in two groups of fertile and infertile patients.&#x0D; Material and Method: This retrospective study examined the electronic records of 170 patients who underwent laparoscopy due to CPPS were included in the study. The patients were divided into two groups: the CPPS and unexplained infertility group (n: 87) as the case group and the CPPS fertile group (n: 83) as the control group. Women aged 25-40 years with unexplained infertility and CPPS were included in the study. &#x0D; Results: Results found a statistically significant association between infertility in women and laparoscopy results (p0.05). There was no statistically significant association between women’s infertility and smoking status (p&gt;0.05). Mann-Whitney test did not find a statistically significant association between case and control regarding age and body mass index (BMI) (p&gt;0.05). There was a statistically significant difference between groups in terms of the duration of pain (p

A comparison between uterine artery blood flow in fertile and unexplained infertile women by Doppler ultrasound using pulsatility index and resistance index

Background and objectives: Infertility is inability to conceive after one year of regular unprotected intercourse. Unexplained infertility is present if the basic fertility investigations are normal. The objective of this study is to investigate the use of uterine artery blood flow as a cause of unexplained infertility (using pulsatility index, resistance index) and compare them to fertile women. Methods: A prospective cohort study was performed on 70 patients (35 fertile and 35 with unexplained infertility patients) in Sulaymaniyah Maternity Teaching Hospital, Kurdistan Region, Iraq, during October 2016 to December 2017. Transvaginal color Doppler ultrasound was done in the mid luteal phase (day 21 - 24) for uterine artery by using pulsatility index and resistance index. Results: The age of the patients ranged from 20 - 39 years. The uterine artery pulsatility index was significantly higher in the unexplained infertile women (mean ± SD = 2.78 ± 0.615) than fertile women (mean ± SD = 2.42 ± 0.325). The uterine artery blood flow resistance index was significantly higher in unexplained infertile group (mean ± SD = 0.899 ± 0.066) than fertile women (mean ± SD = 0.83 ± 0.054). Conclusions: Unexplained infertility is associated with decreased uterine artery blood flow and increase uterine artery resistance (pulsatility index and resistance index) when compared with fertile women.

Kisspeptin: a potential therapeutic target in patients with unexplained infertility?

Kisspeptin has recently emerged as a key regulator of the reproductive axis in women. Kisspeptin, acting centrally via the kisspeptin receptor, stimulates the secretion of the gonadotrophin-releasing hormone (GnRH). To investigate serum kisspeptin levels in infertility patients for its clinical utilisation in management and understanding of the pathophysiology of infertility in a wide array of patients. This prospective case-control study analysis involved 92 primary infertile women with PCOS, diminished ovarian reserve (DOR), unexplained infertility (UEI), and male factor infertility between 20 and 42years of age. Serum samples were collected between the second and fifth day of the menstrual cycle. The kisspeptin level was determined using a human kisspeptin ELISA kit according to the manufacturer's procedure. The median value of serum kisspeptin in the PCOS infertility group was significantly higher than that in the UEI group (p = 0.011). There was a statistically significant (p = 0.015, r = -0.182) negative weak correlation found between serum kisspeptin levels and age. The optimal cutoff value obtained to differentiate the UEI from others (PCOS infertility + DOR + male factor infertility) according to the serum kisspeptin level was 214.3ng/L with a sensitivity of 55% and specificity of 80.9%. Understanding the role of kisspeptin may lead to its use as a biomarker in infertility diagnosis in UEI patients and might guide the use of kisspeptin analogues in selected patients for infertility management.

Association of glutathione s-transferase pi (GSTP1) gene polymorphism in unexplained infertile women

15–20 million people in India are affected by infertility.Among them, 34% of the couples are shown to have unexplained infertility (UEI). Both genetic and environmental factors influence UEI. Data from various studies show that oxidative stress plays an important role in unexplained infertility. The genes of the phase II detoxification enzyme, Glutathione s-transferase family are upregulated in humans as a defense mechanism opposing the adverse effects of oxidative stress and play important role during pregnancy. Since all investigations for infertility work-up are normal evaluating the causes for UEI will have impact on the treatment protocol. In this study the association between GSTP1 variations and unexplained infertility are discussed. To compare the association of GSTP1 polymorphism in women with unexplained infertility and a control group.: This is a case control study with 70 normal ovulatory women who conceived within 12 months of contraceptive free intercourse, and with no history of miscarriage were recruited in the control group and 70 women with unexplained infertility were recruited as study group. All participants included in the study were between 28 and 38 years of age. The association of GSTP1 polymorphism were studied using real-time PCR with the Light Cycler instrument (Roche Applied Science).: GSTP1 variant allele frequencies were 0.39 and 0.41for control and cases respectively. The results of this study indicate GSTP1 genetic polymorphisms did not show a significant association with unexplained infertile group.

Association of infertility cause with perinatal outcomes in a freeze-all policy: an analysis including 10,151 singleton newborns

In vitro fertilization-conceived babies, even singletons, are at a higher risk of poor birth outcomes such as low birthweight and preterm birth than naturally conceived counterparts. It remains unclear as to what extent these adverse outcomes are attributed to the underlying causes of infertility. Evidence on this topic is scarce and has mainly focused on fresh embryo transfer cycles. This study aimed to investigate the effect of infertility cause on perinatal outcomes when a freeze-all strategy is applied. We conducted a retrospective cohort study involving singleton live births born to women who had undergone frozen-thawed embryo transfer during the period from January 2014 to December 2019 at a single center. Subjects were categorized into 7 groups as follows according to the sole cause of infertility: tubal disorder, polycystic ovary syndrome, diminished ovarian reserve, uterine factor infertility, endometriosis, male factor, and unexplained infertility. The perinatal outcomes evaluated were as follows: birthweight, newborn gender, gestational age, preterm birth, low birthweight, small for gestational age, large for gestational age, and macrosomia. Multivariable regression analyses were introduced to control for several important confounders, with unexplained infertility as a reference group. A total of 10,151 women were included for the final analysis. The most common maternal infertility diagnosis of the entire cohort was tubal disorder (42.5%), followed by diminished ovarian reserve (9.5%), endometriosis (9.4%), polycystic ovary syndrome (5.7%), and uterine factor infertility (1.6%). Male factor infertility was present in 19.8% of cycles, and infertility was diagnosed as unexplained in 11.4% of cycles. In the unadjusted analyses, the prevalence of low birthweight (odds ratio, 2.05; 95% confidence interval, 1.24-3.38) and preterm birth (odds ratio, 1.97; 95% confidence interval, 1.33-2.92) was higher among singletons in the polycystic ovary syndrome group than in those from the unexplained infertility group. However, these differences were no longer significant after correction for parental characteristics, treatment variables, and pregnancy complications (adjusted odds ratio, 1.50; 95% confidence interval, 0.98-2.28 for preterm birth; adjusted odds ratio, 1.70; 95% confidence interval, 0.99-2.91 for low birthweight). The risks of preterm birth (adjusted odds ratio, 2.66; 95% confidence interval, 1.53-4.63) and low birthweight (adjusted odds ratio, 3.51; 95% confidence interval, 1.79-6.90) with uterine factor infertility were significantly increased vs the reference group in both unadjusted and adjusted analyses. In addition, the perinatal outcomes in women with other infertility causes were comparable with unexplained infertility in terms of the rates of preterm birth, low birthweight, small for gestational age, large for gestational age, and macrosomia. With the exception of uterine factor infertility, other infertility causes do not seem to compromise perinatal outcomes when compared with unexplained infertility in a freeze-all approach. With the ever-increasing use of frozen-thawed embryo transfer globally, our data hold relevant clinical implications, as they can guide physicians in patient counseling.

O-137 Evaluation of the effect of seminal plasma exosomes from unexplained infertile men on the expression of implantation-related genes

Abstract Study question Do exosomes from seminal plasma of men with unexplained infertility affect endometrial receptivity? Summary answer Seminal plasma exosomes from unexplained infertile men alter the expression of genes and signaling pathways related to endometrial receptivity. What is known already Unexplained infertile Men are a challenging group with no obvious cause of infertility. Many Complicated mechanisms play a crucial role in preparing the receptive endometrium for embryo implantation. The exosomes of seminal plasma are a heterogeneous cargo of nucleic acids, proteins, and lipids that participate in sperm maturation and function by binding to sperm. It is now apparent that the seminal plasma and its exosomes play a complex role in controlling the female reproductive system. There is no study investigating the effect of Unexplained seminal plasma exosomes on endometrial receptivity. Study design, size, duration Samples were collected from 10 men with normal semen parameters from couples undergoing infertility treatment and from 10 donor men with proven fertility and analyzed according to WHO -2010 criteria. Endometrial biopsy tissue was collected from 6 women in the proliferative phase of a natural menstrual cycle. Endometrial epithelial cells were cultured immediately after tissue processing and treated with 100 μg/ml seminal exosomes for (6 and 24 hours); then analyzed for gene expression. Participants/materials, setting, methods Exosomes isolated by an ultracentrifuge and characterized size and ultrastructure with dynamic light scattering and transmission electron microscopy. Western blot analysis showed the presence of the exosome markers. After incubation of exosomes with DiI dye, cytoplasmic localization of exosomes detected by fluorescence microscopy. The endometrial receptivity and signaling pathway genes were analyzed by qRT-PCR and immunocytochemistry. Image J and Prism software were used to quantify and analyze the data. P-value &amp;lt;0.05 was considered statistically significant. Main results and the role of chance Compared with the embryo donation group, the mRNA levels of MUC1, LIF, G-CSF, CX3CL1, and VEGF were significantly downregulated in the endometrium treated with unexplained infertile exosomes, especially after 24 hours of treatment. Mean mRNA levels of IL6, IL8, and TGFB genes in the unexplained infertile group changed compared with the embryo donation group but were not significant (p &amp;gt; 0.05). Immunocytochemical analysis showed that MUC1 and LIFR protein levels were increased in endometrial epithelial cells. Limitations, reasons for caution larger sample size and exosomal compositions assessment will be useful to identify the effect of exosomes on the endometrium. Wider implications of the findings Alterations in the expression of genes associated with endometrial receptivity by exosomes of the unexplained infertile men compared with embryo donation could be one of the causes of infertility in these individuals. Presumably, the atypical composition of exosomes has a different effect on sperm functions and endometrial genes expression. Trial registration number Not applicable

Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility

BackgroundFemale reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women.MethodsWe recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31).ResultCompared with the controls, α-diversity and β-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls.ConclusionThe gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.

Relationship between serum vitamin D levels semen parameters and sperm DNA damage in men with unexplained infertility.

The aim of the study was to investigate the relationship between serum level of vitamin D, semen analysis parameters and sperm DNA damage in men with unexplained subfertility. Fifty-eight men diagnosed with unexplained infertility and 50 age and BMI matched fertile men were included in the study. A participant whose semen parameter is normal but pregnancy is not achieved was accepted as unexplained male infertility. Blood samples were taken from all participants following three-day abstinence for measurement of vitamin D. Sperm DNA damage was assessed by Aniline Blue staining of the collected samples. Compared with the fertile men, male patients with unexplained infertility had significantly lower vit D levels (27.00 ng/mL (12.63-39.30) vs. 23.66 ng/mL (7.50-55.00), p<0.004). While the number of patients with vitamin D levels lower than 20 ng/mL was 26 (44.8%) in the infertile group, it was recorded as 5 (10.0%) in the fertile group (p<0.001). DNA damage was found in 31.50% (9.0-71.0) of the infertile men and 26.00% (11.0-54.0) of the fertile men. DNA damage was found to be significantly higher in the unexplained infertile group (p<0.002). In men with unexplained male infertility, serum vit D levels were positively correlated with total sperm count (r = 0.527, p<0.001), total motility (r = 0.527, p<0.001) and sperm morphology (r = 0.416, p = 0.001). There was a negative and significant correlation between vit D levels and sperm DNA damage (r = -0.605, p<0.001). In the logistic regression analysis, serum vit D > 20 ng/mL led to an improvement in fertility outcome. Men with unexplained infertility exhibit decreased serum vit D levels and increased sperm DNA damage.

Comparison of Treatment outcomes following Ovarian Stimulation with Intrauterine Insemination in Minimal or Mild Endometriosis versus Unexplained Infertility: A Retrospective Cohort Study.

Infertility is a global health issue. The variation in the prevalence of unexplained infertility is attributed to the choice of investigation. There remains a knowledge gap on the impact of minimal and mild endometriosis on treatment outcomes following intrauterine insemination (IUI). The aim of this study was to compare treatment outcomes following ovarian stimulation (OS) and intrauterine insemination (IUI) between minimal and mild endometriosis versus unexplained infertility. A retrospective analysis of women undergoing OS with intrauterine insemination during the year 20142020 in the Department of Reproductive Medicine and Surgery, Christian Medical College, Vellore, was considered for the study. Women with minimal and mild endometriosis or unexplained infertility diagnosed by diagnostic hysterolaparoscopy were included for the analysis. Univariate and multivariate analysis was done. The primary outcome was live birth rate (LBR) per cycle. The secondary outcomes measured were clinical pregnancy rate (CPR) , cumulative LBR (CLBR) per women, cumulative CPR (CCPR) per women and miscarriage rate. The baseline parameters were compared using a t-test for continuous data, and categorical data were compared using the Chi-square/Fisher's exact test as appropriate. The outcomes were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI). There were no significant differences in CPR per cycle (14.28% vs. 18.8%, OR: 0.71; 95% CI: 0.401.28) and LBR per cycle (14.28% vs. 16.6%, OR: 0.84; 95% CI: 0.461.51) between the endometriosis and unexplained infertility groups. The cumulative LBR per woman and CCPR per woman also did not show any significant difference in between the two groups. The current study did not find any significant differences in cumulative LBR and CPR following OS-IUI in women with minimal or mild endometriosis and unexplained infertility.

What are the factors affecting IVF success in women with hypogonadotropic hypogonadism?

This study aimed to investigate in vitro fertilization (IVF) outcomes in women with hypogonadotropic hypogonadism (HH) and unexplained infertility and investigate factors affecting the pregnancy rate among HH patients. This retrospective cohort study was conducted at Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital, Turkey, a tertiary care referral center. The medical records of 143 women who underwent IVF treatment at this hospital between 2015 and 2020 were reviewed. Sixty-three had hypogonadotropic hypogonadism (HH) and 74 had unexplained infertility. Demographics, hormonal profile, IVF cycle characteristics, and pregnancy rates were recorded. The factors affecting the ongoing pregnancy rates were evaluated among HH patients. Anti-Mullerian hormone (AMH) levels were lower among women with HH compared to those with unexplained infertility (1.64±1.2 vs. 3.0±2.13). IVF cycle characteristics and ongoing pregnancy outcome (20.28% vs. 22.97%) were similar between the groups; however, the total dose of human menopausal gonadotrophin (HMG) used (5127.74±1845.8 vs. 2035.71±1387.45) was higher in the HH group. Increased estradiol level (2596.35±1085 vs. 1869.9±1203.4), endometrial thickness (10.82±1.74 vs. 8.43±2.33), higher number of total oocytes retrieved (12.14±4.34 vs. 8.43±5.44) were correlated with higher ongoing pregnancy rates among the HH group. IVF success rates were similar between the HH and unexplained infertility groups. Although AMH level was not a prognostic factor for IVF success, higher doses of HMG were needed to achieve pregnancy in the HH group. The factors affecting the ongoing pregnancy rates in the HH group were higher estradiol level, increased endometrial thickness, and a higher number of oocytes retrieved.

Role of prolidase activity and oxidative stress biomarkers in unexplained infertility

Our aim was to explore the significance of serum prolidase enzyme activity and oxidative stress in women with unexplained infertility (UEI). In this case-control study (n=160; 86 cases; 74 controls) prolidase enzyme activity and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and vitamin E were measured in plasma using enzyme-linked immunosorbent assays. Prolidase enzyme activity and TAS levels were particularly higher in the patient group (P=0.013, P=0.001, respectively). Decreased OSI levels were detected in the patient group (P=0.001). There was a positive relationship of prolidase with vitamin E in both patient and control groups (r=0.892, P=0.001, and r=0.659, P=0.001, respectively). A positive, but weak, relationship was identified between prolidase activity and TOS levels and also between vitamin E and TOS levels in the UEI group (r=0.265, P=0.049, and r=0.288, P=0.014, respectively). No association was found between prolidase and TOS levels or between vitamin E and TOS levels in the control group (r=0.0097, P=0.527, and r=0.085, P=0.610, respectively). Our results showed an association between serum prolidase activity and oxidative stress in UEI patients. Further studies including greater groups are required to show the role of reactive oxygen species in UEI.

P–625 Does endogenous progesterone play a role in unexplained infertility? A systematic review

Abstract Study question Does endogenous progesterone play a role in unexplained infertility? A systematic review investigating the possibility of altered progesterone-mediated change leading to reduced endometrial receptivity in women with unexplained infertility. Summary answer The evidence suggests that many of the measurable actions of endogenous progesterone are reduced in women with unexplained infertility when compared with controls. What is known already Unexplained infertility is the diagnosis given to heterosexual couples who fail to conceive despite normal semen analysis, regular ovulation and patent tubes. The underlying pathology is likely to relate to embryonic failure to implant. Endometrial receptivity is largely mediated by luteal phase progesterone which controls many different molecular pathways involved in secretory transformation. It is possible that defective actions of progesterone could contribute to this condition. To date however, there is minimal published literature on the role of progesterone in unexplained infertility. We therefore felt it important to combine the results of all trials measuring progesterone-related outcomes in unexplained infertility. Study design, size, duration A systematic review was performed using standard Cochrane methodology. We searched Medline, Embase and CINAHL databases from inception to December 2020 and additionally hand-searched. The study was prospectively registered on Prospero (CRD42020141041). The search strategy was designed to identify all types of primary research published in English that investigated women with unexplained infertility and reported outcomes that relate to progesterone. Newcastle Ottawa Scoring and NHLBI assessment of bias scoring was performed. Participants/materials, setting, methods The study population was women with unexplained infertility. Included studies had no controls, fertile controls or controls with other diagnoses associated with subfertility. Outcomes were either upstream affecting progesterone production/release or receptor expression or downstream measuring results of progesterone-mediated processes. The results were summarised in a narrative review. Meta-analysis was not possible due to varying methodological heterogeneity. Main results and the role of chance 36 studies were included. No difference was found in 18 studies in progesterone levels (serum, peritoneal and salivary) between women with unexplained infertility and control groups. Despite this, 32 of the 36 included studies demonstrated a significant difference between progesterone-mediated outcomes in the unexplained infertile and control groups. 5 ultrasound studies all reported increased resistance and decreased flow on doppler studies of uterine, ovarian and spiral arteries and reduced endometrial and sub-endometrial perfusion. No significant difference was found in luteal phase endometrial thickness in 2 studies. Endometrial dating was reported by 11 studies. 8/11 studies reported significantly higher numbers (20–38%) of ‘out-of-phase’ endometrium in women with unexplained infertility compared with controls. Endometrial biopsy results measuring different cell adhesion molecules, monoclonal antibodies and other molecules involved in endometrial transformation as well as expression of responsible genes and steroid hormone receptors were included. All the progesterone-mediated outcome measures listed above were reduced in unexplained infertile women except β3 integrin which reported contradictory results and SGK1 expression which was reported in 1 study. This trend towards support for the hypothesis may be more important than any individual finding. The quality of the included studies was variable and hence the strength of the recommendations moderate. Limitations, reasons for caution The number of studies measuring each outcome was limited. The study quality varied from good to poor. Methodological heterogeneity between studies prevented meta-analysis. The strength of the study however comes from the originality of the research, the variety of included outcomes and that 32/36 papers reported results supporting the hypothesis. Wider implications of the findings: The findings of this systematic review support the need for larger, well designed research on this topic. If altered progesterone-mediated receptivity is implicated in unexplained infertility, it may be possible to offer other therapeutic interventions to improve outcomes as an alternative or adjunct to standard fertility treatment. Trial registration number NA