Search

Male factors may be present in up to 50–70% of infertile couples and the prevalence of male infertility accounts for 20–30% of infertility cases. Understanding the mechanisms and causes behind male infertility remains a challenge, but new diagnostic tools such as DNA fragmentation might aid in cases where the routine semen analysis is insufficient. DNA fragmentation, which refers to damages or breaks of the genetic material of the spermatozoa, is considered one of the main causes of male infertility due to impaired functional capability of sperm. The aim of the present narrative review is to investigate and enlighten the potential correlation between DNA fragmentation and male infertility parameters such as the seminal profile and the reproductive outcomes. Comprehensive research in PubMed/Medline and Scopus databases was conducted and 28 studies were included in the present review. Fourteen studies provided data regarding the impact of DNA fragmentation and seminal parameters and showed a correlation of significantly lower sperm count, lower concentration, motility, and abnormal morphology with an increased DNA fragmentation index (DFI). Similarly, 15 studies provided data regarding the impact of DFI on reproductive outcomes. Two studies showed higher aneuploidy rates with higher DFI values, and seven studies showed significantly lower pregnancy rates and live birth rates with higher DFI values. Ultimately, the studies included in this review highlight, collectively, the importance of measuring sperm DFI in the assessment of male infertility. Further studies are needed to explore the effectiveness of interventions aiming to reduce DFI levels. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to compare the inflammatory markers in patients who had ovu-lation induction with clomiphene citrate (CC) and who underwent intrauterine insemi-nation (IUI) due to unexplained infertility in patients who could get pregnant and who could not. Materials and Methods: The study included 125 females with unexplained infertility who underwent ovulation induction with CC and who underwent IUI at the Health Sciences University Ankara Etlik Zübeyde HanımGynecology Training and Research Hospital Assisted-Reproduction Therapy Clinic between July 2019 and December 2019. Of the patients, 104 (83.2%) of them could not get pregnant as a result of IUI, and 21 (16.8%) females got pregnant. Hemogram parameters collected from patients on the day of IUI were recorded. Results: In terms of age, infertility duration, BMI, gravida, parity, number of living children, abortion and stillbirth numbers, no statistically significant difference was found between the two patient groups which were created based on getting pregnant or not (p>0.05). No significant difference was found between the groups in terms of se-rum estrogen, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), prolactin, and antimullerian hormone (AMH) levels, hemoglobin, white blood cell count, neutrophil count, lymphocyte count, platelet count, MPV, CRP, and P/ (p>0.05). A statistically significant difference was found in terms of N/L (p<0.05). The N/L ratio was found to be higher in the group whose members could not get pregnant after IUI compared to the group whose members could get pregnant after IUI. Conclusion: We found that increased N/L is a marker that may negatively affect IUI success. According to these results, we believe that increased inflammation and throm-bosis may negatively impact pregnancy rates. When beginning treatment with assisted reproductive technology, hemogram parameters can be used as a guide as a simple and routine examination to predict pregnancy success, and it is a cost-effective method. However, larger series of studies and other inflammatory markers are needed. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is IVF indicated for couples with age-related infertility? SUMMARY ANSWER IVF may be of doubtful utility for age-related infertility. WHAT IS KNOWN ALREADY A diagnosis of unexplained infertility is drawn when the diagnostic work-up fails to identify any patent cause. Although typically managed uniformly, unexplained infertility is likely to comprise a wide range of conditions, including age-related infertility (at least in older women). Unfortunately, no validated tests for the identification of age-related infertility exist and these women are typically treated as unexplained cases. However, homologous ART may be less effective for these women because these techniques may be unable to treat the detrimental effects of ageing on oocyte competence. STUDY DESIGN, SIZE, DURATION Women aged 18–42 years who underwent IVF procedures between January 2014 and December 2021 were selected retrospectively. In the first part of the study, we aimed to assess whether the proportion of women with unexplained infertility (i.e. without patent causes of infertility) increased with age. In the second part of the study, women with unexplained infertility were matched 1:1 by age, study period, and duration of infertility, to those with a patent cause of infertility. If our hypothesis is valid, the first part of the study should highlight an increase in the proportion of unexplained infertility with age. Moreover, in the second part of the study, one should observe a sharper decrease in the rate of IVF success of the procedure with age in women with an unremarkable work-up compared to those with a definite cause of infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS Women were included if: they had been trying to conceive for more than 2 years, they had retrieved more than three oocytes, and had not undergone previous IVF attempts. We exclude couples with severe male factor (criptozoospermia), chronic anovulation, untreated hydrosalpinx, or intracavitary diseases. The first part of the study aimed at investigating the relative proportion of unexplained infertility with age. The outcome of the second part was the distribution of the live births between unexplained versus explained infertility, in women younger or older than 35 years. Only the results of the first IVF cycle were considered (including both fresh and frozen cycles). The live birth rate corresponded to the cumulative chance of a live birth per oocyte retrieval. MAIN RESULTS AND THE ROLE OF CHANCE One thousand five hundred and thirty-five women were selected for the first part of the study; 742 of them had unexplained infertility (48%). The frequency of this diagnosis was lower among women aged <35 years (40%) compared to those ≥35 years (52%) (P  < 0.001). A clear gradient emerged when considering smaller intervals of age (P  < 0.001). A total of 1134 women (567 unexplained cases and 567 explained cases) were selected for the second part of the study. Baseline variables were comparable between women with unexplained and explained infertility. Among women younger than 35 years (n = 229 unexplained cases and 229 explained cases), 108 live births were observed in women with unexplained infertility (47%) and 88 in those with explained infertility (38%). In comparison, among women older than 35 years, the live births occurred in 90 (27%) and 114 (34%) couples, respectively (P  = 0.03). The adjusted odds ratio (OR) for a live birth in older women with unexplained infertility was 0.63 (95% CI: 0.43–0.94). In other words, the effectiveness of IVF in older women with unexplained infertility is reduced by an additional 37% when compared to women of similar age with a patent cause of infertility. Moreover, when considering smaller intervals of age, a gradient of the adverse effect of age on the distribution of live births between unexplained and explained infertility emerged (P  = 0.003). Overall, these results support the hypothesis that IVF may be of modest benefit in women with age-related infertility. The decline in IVF success is sharper in women with unexplained infertility compared to those with explained infertility, indirectly suggesting that IVF cannot effectively treat age-related infertility. LIMITATIONS, REASONS FOR CAUTION We postulated that the greater decline in IVF success with age in the unexplained group could be related to the concomitant increase in the proportion of women with age-related infertility. However, even if this is theoretically logical, the unavailability of validated tools to diagnose age-related infertility makes our inference speculative. We cannot exclude that the prevalence of other unknown causes of infertility that cannot also be effectively overcome with IVF could increase with age. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that IVF may be of modest utility for treating age-related infertility. Offering this procedure to older women with an unremarkable infertility work-up may be questioned. However, the diagnosis of age-related infertility remains challenging and identifying a biomarker that could reliably diagnose age-related infertility is a priority. STUDY FUNDING/COMPETING INTEREST(S) The study was partially funded by the Italian Ministry of Health—current research IRCCS and by a specific grant supported by Ferring. ES declares receiving honoraria for lectures at meetings from IBSA and Gedeon-Richter and he also handles private grants of research from Ferring, IBSA, Theramex, and Gedeon-Richter. All the other authors do not have any conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Abstract The studies posits that there is not sufficient evidence to support the use of intrauterine platelet-rich plasma (PRP) infusion in patients with recurrent implantation failure (RIF). This study aims to investigate the effects of infusion of PRP on patients with unexplained-RIF in fresh and frozen embryo transfer (ET) cycles. A total of 80 participants were included in this study. The participants were randomly assigned to one of two groups with and without PRP infusion. Each of the PRP and control groups were also divided into fresh and frozen ET subgroups. ET outcomes were compared between groups. Clinical pregnancy rate was significantly higher in Frozen ET in PRP group than other subgroups (p

Abstract Objective This study aimed to assess the effect of sildenafil citrate and estradiol valerate as adjuvant therapy during ovarian stimulation cycles with clomiphene citrate in patients with unexplained infertility in Kisangani. Method A double-blind, randomized controlled trial was conducted for two years at two specialized health facilities in Kisangani (University Clinics of Kisangani and “Clinique des Anges Kisangani”). The population included 148 patients, 74 of whom were on clomiphene citrate + sildenafil citrate (CCSC) regimens and 74 of whom were on clomiphene citrate + estradiol valerate (CCEV) regimens for three months. The primary indicator was the conception rate, with secondary outcomes encompassing endometrial thickness, appearance and vascularity, the number of mature follicles and ovulation rate. Results The two groups were comparable in terms of sociodemographic and clinical characteristics. The mean duration of attempting to conceive was 4.39 years versus 4.36 years (P = 0.839), while the mean AFC was 11.51 versus 11.46 (P = 0.831), in the CCSC group versus CCEV group respectively. Secondary infertility was the most frequent diagnosis in each of the two groups. The biochemical pregnancy rate was comparable between the two groups (P = 0.385), while the clinical pregnancy rate was significantly higher in the CCSC group versus CCEV group (P = 0.04). Both perifollicular flow and the ovulation rate were significantly higher in the CCSC group versus the CCEV group (P = 0.006 and P = 0.002 respectively). However, endometrial vascularity/thickness, and the number of Graafian follicles were not significantly different between the two groups. Conclusion As an adjuvant, sildenafil increases the rate of clinical pregnancy more than does estradiol in patients with unexplained infertility undergoing ovarian stimulation with clomiphene citrate. Study registration PACTR 202,310,849,449,401 (Pan African Clinical Trials Registry).

Objective: To compare cumulative live birth rate (CLBR) and cost-effectiveness of intracytoplasmic sperm injection (ICSI) vs. conventional in vitro fertilization (cIVF). Design: Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Setting: Society for Assisted Reproductive Technology (SART) member IVF clinics in the United States. Patient(s): Patients with unexplained infertility who underwent first autologous retrieval cycles between January 2017 and December 2019 with linked fresh and frozen embryo transfers through December 2021. Intervention(s): ICSI vs. cIVF. Main Outcome Measure(s): The primary outcome was CLBR, defined as ≤1 live birth from a retrieval cycle and all linked embryo transfers. Secondary outcomes included two pronuclear (2PN) per oocyte retrieved, miscarriage rate, and total number of transferred or frozen embryos per 2PN. Subsamples with and without preimplantation genetic testing for aneuploidy (PGT-A) were analyzed. Outcomes were adjusted for age, body mass index, number of oocytes retrieved, length of follow-up, and clinic ICSI use rate. Result(s): A total of 18,805 patients with unexplained infertility were included. No difference in CLBR was found among cycles without genetic testing (54.4% ICSI vs. 57.5% cIVF) and with PGT-A (47.6% ICSI vs. 51.8% cIVF). Intracytoplasmic sperm injection cycles without genetic testing had a higher miscarriage rate (16.4% vs. 14.4%) but no difference was seen in cycles with PGT-A (13.9% ICSI vs. 13.2% cIVF). Intracytoplasmic sperm injection cycles had a significantly lower ratio of 2PN per oocyte retrieved without genetic testing (59.7% vs. 60.9%) and with PGT-A (63.3% vs. 65.8%). The ratio of embryos transferred or frozen per 2PN was not significantly different in cycles without genetic testing (49.4% vs. 49.6%) or with PGT-A (54.2% vs. 55.2%). Total fertilization failure occurred in 216 patients (4%) who underwent cIVF and in 153 patients (1.1%) who used ICSI.Compared with cIVF alone, an estimated additional $11,011,500 was charged to patients for ICSI without genetic testing and $9,010,500 was charged to patients for ICSI with PGT-A over 2 years by Society for Assisted Reproductive Technology clinics. On the basis of total fertilization failure rates, 35 patients would require treatment with routine ICSI to avoid a single cycle of total fertilization failure with cIVF. Conclusion(s): Routine use of ICSI in unexplained infertility is not warranted due to the additional cost and lack of CLBR benefit.

Introduction: The specialists refer unexplained infertility to the so-called diagnosis of exclusion due to the fact that in the process of medical examination of married couples the causes of infertility cannot be established. Material and methods: The clinical characteristics and embryological features of in vitro fertilization programs of couples with unexplained infertility versus the patients with tuboperitoneal infertility were analyzed retrospectively and prospectively. The study group comprised 93 women, who underwent 108 in vitro fertilization programs, and the control group consisted of 45 patients, who underwent 49 in vitro fertilization programs. Results: Significant differences (p<0.05) were found between the groups in anamnestic, clinical, laboratory, and instrumental characteristics. The ovarian stimulation protocols were comparable between the groups of patients. The blastulation rate was considered to be the endpoint in in vitro fertilization programs, and it was significantly lower in the group of women with unexplained infertility (45.53%). In-depth analysis of the embryonic stage of in vitro fertilization programs showed, that low blastulation rate in unexplained infertility was mainly due to the fact that embryos stopped developing about three days after they were cultured. At the same time the morphological assessment showed that the quality of blastocysts was higher in the group of unexplained infertility (66.7%) compared to the group of tuboperitoneal factor of infertility (45.8%). Preimplantation genetic testing for aneuploidy showed similar frequency of detection of euploid embryos (41.7% and 40.0%, respectively). Conclusion: A "clinical portrait" of women with unexplained infertility was described. The low blastulation rate was noted in in vitro fertilization programs for women with unexplained infertility. Given the identified impairments of early embryonic development in unexplained infertility, it is appropriate to recommend the patients to undergo early use of in vitro fertilization with good-quality embryo transfer (>3, AA, AB, BA according to Gardner grading system) on day 5-6 of culture without long-lasting preliminary examination and empirical treatment. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)? SUMMARY ANSWER Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group. WHAT IS KNOWN ALREADY Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied. STUDY DESIGN, SIZE, DURATION The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors. MAIN RESULTS AND THE ROLE OF CHANCE Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles. LIMITATIONS, REASONS FOR CAUTION The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle. WIDER IMPLICATIONS OF THE FINDINGS Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles. STUDY FUNDING/COMPETING INTEREST(S) Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc. and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate whether there is a difference between the results of intracytoplasmic sperm injection (ICSI) pregnancies and subsequent spontaneous pregnancies with a diagnosis of unexplained infertility. Material and Methods: In this retrospective study, a total of 48 women who first conceived with ICSI and then achieved spontaneous pregnancy were included. Duration and causes of infertility, time to spontaneous conception, pregnancy outcomes, and maternal and neonatal complications were evaluated. Results: Maternal age was older in the spontaneous pregnancy group compared to the ICSI group (p=0.029). The gestational age at delivery was found similar in both groups. Although birth weight was higher in the spontaneous pregnancy group, the difference between the groups was not statistically significant (p=0.382). The time to achieve pregnancy was shorter in the spontaneous pregnancy group (p=0.001). Gestational diabetes was significantly higher in the spontaneous pregnancy group (p=0.001), while amniotic fluid abnormality, gestational hypertension (p=0.001), and preterm delivery (p=0.001) were significantly higher in the ICSI group. While the number of babies with the 1st-minute low Apgar score was higher in the ICSI group (%4.16 vs 2.08%, p=0.001), the 5th-minute Apgar score was similar. Conclusion: Even if couples are evaluated as infertile, it should be taken into consideration that they can achieve spontaneous pregnancy. It may be rational to wait for spontaneous pregnancy in eligible couples with unexplained infertility and not to refer the patient for early assisted reproductive techniques. [ABSTRACT FROM AUTHOR]

Purpose: This study estimates the need of IVF/ICSI in Australia as compared to its actual uptake. Methods: We created a model estimating for the annual demand for IVF/ICSI in a hypothetical infertile population, using demographic data from medical literature and Australian government databases. For each category of infertility (tubal, severe male, endometriosis, anovulation and unexplained), our estimated need for IVF/ICSI was compared to the actual IVF/ICSI uptake (ANZARD 2019). The model consisted of three categories depending on couples' cause of infertility, i.e. couples with absolute indications for IVF/ICSI (couples with severe male factor infertility and tubal obstruction); couples with anovulatory infertility (couples with ovulation disorders) and couples with ovulatory infertility (couples suffering from unexplained infertility and endometriosis). The model was applied to each of these categories to determine the number of couples that would require IVF/ICSI treatment after failing to conceive naturally or after following alternative treatment plans. The main outcomes of this study were the estimate of IVF/ICSI cycles and the difference between the estimate and the reported number of IVF/ICSI cycles (2019 ANZARD report). Results: We estimated that approximately 35,300 couples required IVF/ICSI treatment in Australia in 2019, while in 2019 according to ANZARD, 46,000 couples underwent IVF/ICSI. A higher uptake of IVF/ICSI cycles than expected was specifically reported in couples with unexplained infertility, ovulation disorders and endometriosis, while for tubal and severe male infertility uptake seemed adequate. Conclusion: In Australia, there seems to be overservicing of IVF/ICSI, specifically for unexplained, ovulatory and endometriosis-related infertility. [ABSTRACT FROM AUTHOR]

Background Unexplained infertility (UEI) is a complex pathological condition that involves environmental and genetic factors. Hashimoto's thyroiditis (HT) is the most common autoimmune disease in reproductive-age women. Circular RNAs (circRNAs) play a biological role in autoimmunity by regulating gene transcription. A previous study found upregulation of hsa_circ_0089172 in HT. We aimed in the current research to investigate the relative expression level of hsa_circ_0089172 in patients with HT and to assess its correlation with UEI among Egyptian women. Methods: Among 60 women with HT (35 fertile and 25 women with UEI) and 60 healthy subjects as the control group. all subjects were investigated in clinical, laboratory, and radiological. Hsa-circ-0089172 was examined by RT-PCR. Results: There were significantly higher values of hsa_circ_0089172 in UEI group (3.4±0.26) compared to fertile group (2.34±0.33) and control group (0.91±0.216), P <0. 001. Interestingly we observed that anti-TPO and anti TG values were the independent factors associated with hsa_circ_0089172 in the prediction of UEI. hsa_circ_0089172 exposed a significant predictive value of HT, with an AUC of 0.990 (C. I=0.973-1.000), sensitivity of 91.7%, and specificity of 87.1%. Regarding the prediction of UEI among women with HT, the AUC of hsa_circ_0089172 was 0.994(C.I=0.981-1.000), a sensitivity of 94.9%, and a specificity of 89. 3%, P <0 .001 Conclusions: hsa_circ_0089172 level was upregulated in HT patients, particularly patients with UEI. Moreover, it was positively correlated with TSH, anti-TPO, and anti-TG [ABSTRACT FROM AUTHOR]

Background: There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta‐analysis and best practice advice. Objectives: This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis. Search strategy: CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language. Data collection and analysis: Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range. Main results: Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid‐luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies. Conclusions: This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care. Linked article: This article is commented on by Tarek El‐Toukhy, pp. 898 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17778 [ABSTRACT FROM AUTHOR]

Background: In Egypt, where research into the underlying cytogenetic and molecular causes of infertility is scarce, unexplained infertility presents a substantial clinical and emotional difficulty for many couples. This study attempts to fill a gap in knowledge on the chromosomal disorders that cause infertility in Egyptian couples. Methods: In order to compile research on cytogenetic and molecular anomalies in Egyptian couples with unexplained infertility, an extensive database search was performed. Translocations, inversions, and aneuploidies were the primary focus of this study. Studies discussing the diagnostic utility of chromosomal analysis and molecular markers were considered and critically appraised up to April 2023 for this review. Results: The results suggest that cytogenetic and molecular abnormalities are responsible for a significant proportion of unexplained infertility in Egypt. Disruption of gametogenesis, abnormal embryonic development, and problems with genomic imprinting have all been linked to chromosomal abnormalities, which are typically missed in routine infertility examinations. Improved understanding of the causes of infertility and the potential for individualized therapies has resulted from the development of genetic testing. Conclusions: There is a strong correlation between cytogenetic and molecular abnormalities and unexplained infertility in Egypt. It becomes clear that karyotypic and molecular chromosomal examination are essential parts of the diagnostic process for afflicted couples. This analysis highlights the need for improved diagnosis techniques and the creation of individualized treatments. The ethical implications of genetic testing and Assisted reproductive technology are substantial, calling for a careful weighing of technology advantages and moral issues. New genetic and chromosomal therapies show promise in reducing infertility problems, and they fit in with current trends in ethics, medicine, and scientific inquiry. Future Directions: Future research in reproductive genetics should aim to improve diagnosis accuracy and provide therapies that are targeted to individual genetic profiles. There is a need for both ethical norms and instructional initiatives to help couples make informed choices about genetic testing and reproductive treatments. [ABSTRACT FROM AUTHOR]

Liang Lu,1,&ast; Yan Lu,2,&ast; Longyi Zhang2 1Department of Reproductive Center, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, People’s Republic of China; 2Clinical Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Longyi Zhang, Clinical Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, People’s Republic of China, Tel +86 15267914600, Email happy_zhang1y@163.comPurpose: Female infertility is a global health concern. The aim of this study was to investigate the relationship between regulatory T (Treg) cells and helper T cells 17 (Th17) in peripheral blood and unexplained infertility (UI). In addition, we explored potential valuable diagnostic biomarkers for patients with UI and ascertained whether Treg and Th17 cells are associated with primary and secondary UI.Patients and Methods: The patients underwent standard fertility evaluation test, including blood tests, ultrasound examination, fallopian tube tests, ovulation assessment, and male partner’s semen analysis. According to the inclusion and exclusion criteria, this study enrolled 37 patients with UI (30 with primary UI and 7 with secondary UI) and 26 age-matched healthy volunteers as the control group. Flow cytometry was used to detect the frequency of Treg and Th17 cells. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was used to assess the diagnostic performance. An AUC > 0.800 indicated good diagnostic performance.Results: The percentage of Treg decreased significantly, whereas the percentage and absolute count of Th17 cells increased. Moreover, the Th17/Treg ratio in patients with UI increased significantly. As a diagnostic biomarker for UI, the Th17/Treg ratio exhibited remarkable diagnostic performance (AUC: 0.813 (95% CI = 0.709– 0.917)). However, the percentages and absolute counts of Treg and Th17 cells in the peripheral blood of women with primary and secondary UI, as well as their Th17/Treg ratios, did not differ significantly.Conclusion: The distribution of Treg and Th17 cells is imbalanced in patients with UI. Therefore, the Th17/Treg ratio may be a promising indicator of UI. However, there were no significant differences in the distribution of Treg and Th17 cells between women with primary and secondary UI.Keywords: female infertility, regulatory T cell, T helper 17 cell, unexplained infertility, immunology, biomarkers

Abstract Objectives The endometrium of most unexplained infertility (UI) patients has been altered histologically. Shear wave elastography (SWE) is utilized to assess the signature of living tissue. This study aimed to explore the value of SWE in evaluating endometrial receptivity (ER) in UI patients. Methods In total, 59 UI patients (UI group) and 52 normal control women (NC group) who received fertility consultation in our hospital were included between January 2022 and June 2023. We divided them into the late-proliferative phase of UI group (LPUI; n = 59), mid-secretory phase of UI group (MPUI; n = 41), late-proliferative phase of NC group (LPNC; n = 52), and mid-secretory phase of NC group (MPNC; n = 45). Transvaginal ultrasonography and SWE were performed during the LP and MP. Endometrial thickness (EMT), uterine artery pulsatility index (UA-PI), endometrial mean elasticity (E-mean), and mean shear wave velocities (SWV-mean) were measured. Results There were significant differences in E-mean, SWV-mean, EMT, and UA-PI between the UI group and the NC group during both the LP and MP (p MPNC vs MPUI < 0.05, p LPNC vs LPUI < 0.05). E-mean and SWV-mean decreased with increasing EMT but increased with increasing UA-PI (p < 0.05). The most effective parameter for evaluating ER in UI patients is the E-mean (AUC = 0.89). Conclusions UI patients exhibited thinner endometrium, increased endometrial stiffness, and poor endometrial blood perfusion. E-mean was the most effective parameter to evaluate ER in UI patients. The study preliminarily proved that SWE is a promising non-invasive tool for evaluating the condition of endometrium. Critical relevance statement This study aimed to explore the significance of endometrial elasticity measured by SWE in evaluating patients with UI. The findings revealed a correlation between EMT, UA-PI, and E-mean. Endometrial elasticity can serve as an effective indicator for predicting ER. Key points 1. To explore the significance of endometrial elasticity in assessing patients with UI. 2. The endometrium of UI patient exhibited thinness, stiffness, and poor blood perfusion. 3. Endometrial elasticity serves as a valuable indicator for evaluating endometrial receptivity. Graphical Abstract

BACKGROUND: Unexplained infertility is associated with a higher abortion rate and lower fertilization rate, implantation rate, clinical pregnancy rate and cumulative live birth rate. It is urgent to establish a clinical prediction model related to infertility of unknown cause to solve the problems of clinical prognosis and individualized medical services, and finally achieve the purpose of increasing the cumulative live birth rate of patients with infertility of unknown cause. OBJECTIVE: To construct and verify the prediction model of high-quality blastocyst formation in patients with unexplained infertility during in vitro fertilization. METHODS: A total of 419 patients with unknown infertility who underwent in vitro fertilization in the Assisted Reproduction Department of Changzhou Maternal and Child Health Care Hospital from March 2017 to June 2022 were retrospectively analyzed, including 317 patients with high-quality blastocysts and 102 patients without high-quality blastocysts. A prediction model was established and used as the model group. The model group was sampled 1 000 times by the Bootstrap method as the validation group. Firstly, the univariate analysis was used to screen the influencing factors of high-quality blastocyst formation of unknown infertility, and the best matching factors were selected by the least absolute shrinkage and selection operator (LASSO) algorithm. Multiple factors were included in the progressive Logistic regression to find out the independent influencing factors and draw a column graph. Finally, the subject working curve, calibration curve, clinical decision curve and clinical impact curve were used to verify the differentiation and accuracy of the prediction model as well as the clinical application efficiency. RESULTS AND CONCLUSION: (1) Univariate analysis of the factors influencing the formation of high-quality blastocyst of unknown infertility were age, insemination method, antimullerian hormone level, basal follicle-stimulating hormone level, basal luteinizing hormone level, human chorionic gonadotropin injection day follicle-stimulating hormone level, human chorionic gonadotropin day estradiol level, progesterone level on human chorionic gonadotropin day, the number of high-quality cleavage embryo (day 3) and the number of blastocyst formation (P < 0.05). (2) The best matching factors further screened by LASSO regression were age, insemination method, antimullerian hormone level, basal luteinizing hormone level, human chorionic gonadotropin injection day follicle-stimulating hormone level, human chorionic gonadotropin day estradiol level, the number of high-quality cleavage embryo (day 3) and the number of blastocyst formation (P < 0.05). Multifactor stepwise Logistic regression results showed that independent influencing factors on the formation of high-quality blastocysts for unexplained infertility were age, insemination method, antimullerian hormone level, the number of high-quality cleavage embryo (day 3), and the number of blastocyst formation. (3) Receiver operating characteristic curve exhibited that the area under the curve was 0.880(0.834, 0.926) in the model group and 0.889(0.859, 0.918) in the validation group. It showed that the prediction model had good differentiation. The average absolute error of the calibration curve was 0.036, indicating that the model had good accuracy. The Hosmer-Lemeshow test showed that there was no statistical difference between the prediction probability of blastocyst formation and the actual probability of blastocyst formation (P > 0.05). The clinical decision curve and clinical impact curve showed that the model group and the validation group had the maximum clinical net benefit when the threshold probability value was (0.16-0.96) and (0.08-0.93), respectively, and had better clinical application efficacy within the threshold probability range. These findings concluded that age, insemination method, antimullerian hormone, the number of highquality cleavage embryos (day 3), and the number of blastocyst formation were independent factors influencing the formation of the fine blastocyst in patients with unexplained infertility. The clinical prediction model constructed by these factors has good clinical prediction value and clinical application efficiency and can provide a basis for clinical prognosis and intervention as well as the formulation of individual medical programs. [ABSTRACT FROM AUTHOR]

The diagnosis of unexplained infertility presents a dilemma as it signifies both uncertainty about the cause of infertility and the potential for natural conception. Immediate treatment of all would result in overtreatment. Prediction models estimating the likelihood of natural conception and subsequent live birth can guide treatment decisions. To evaluate if in couples with unexplained infertility, prediction models are effective in guiding treatment decisions. This review examines 25 studies that assess prediction models for natural conception in couples with unexplained infertility in terms of derivation, validation, and impact analysis. The largest prediction models have been integrated in the synthesis models of Hunault, which includes female age and infertility duration, having been pregnant before and motile sperm percentage. Despite its limited discriminative capacity, this model demonstrates excellent calibration. Importantly, the impact of the Hunault model has been evaluated in randomized clinical trials, and shows that in couples with unexplained infertility and 12-month natural conception chances exceeding 30%, immediate treatment with intrauterine insemination (IUI) and controlled ovarian hyperstimulation is not better than expectant management for 6 months. Below the threshold of 30%, treatment with IUI is superior over expectant management, but immediate in vitro fertilization was not better than IUI. In couples with unexplained infertility and a good prognosis for natural conception, treatment can be delayed, whereas in couples with a poor prognosis, immediate treatment (with IUI-controlled ovarian hyperstimulation) is warranted. These data indicate that in couples with unexplained infertility, integration of prediction models into clinical decision making can optimize treatment selection and maximize fertility outcomes while limiting unnecessary treatment. [ABSTRACT FROM AUTHOR]

This document highlights the challenges of diagnosing and treating unexplained infertility in heterosexual couples, emphasizing the need for advancements in diagnostic tests and individualized decision-making. The document also mentions a study that found intrauterine insemination with ovarian stimulation (IUI-OS) to be more effective in achieving live births compared to expectant management. It emphasizes the importance of accurately assessing coital frequency and timing, considering lifestyle factors, and developing better diagnostic tools. Further research is needed to improve treatment options and prognostic models for unexplained infertility. [Extracted from the article]

Introduction: Infertility affects 8-12% of couples worldwide, with 15-30% classified as unexplained infertility (UI). Thyroid autoimmunity (TAI), the most common autoimmune disorder in women of reproductive age, may impact fertility and pregnancy outcomes. However, the underlying mechanism is unclear. This study focuses on intrauterine insemination (IUI) and its potential association with TAI in UI patients. It is the first meta-analysis following a comprehensive literature review to improve result accuracy and reliability. Methods: Retrospective cohort study analyzing 225 women with unexplained infertility, encompassing 542 cycles of IUI treatment. Participants were categorized into TAI+ group (N=47, N= 120 cycles) and TAI- group (N=178, N= 422 cycles). Additionally, a systematic review and meta-analyses following PRISMA guidelines were conducted, incorporating this study and two others up to June 2023, totaling 3428 IUI cycles. Results: Analysis revealed no significant difference in independent variables affecting reproductive outcomes. However, comparison based on TAI status showed significantly lower clinical pregnancy rates (OR: 0.43, P= 0.028, 95%CI: 0.20-0.93) and live birth rate (OR: 0.20, P= 0.014, 95%CI: 0.05 ~ 0.71) were significantly lower than TAI- group. There was no significant difference in pregnancy rate between the two groups (OR: 0.61, P= 0.135, 95%CI: 0.32-1.17). However, the meta-analysis combining these findings across studies did not show statistically significant differences in clinical pregnancy rates (OR:0.77, P=0.18, 95%CI: 0.53-1.13) or live birth rates (OR: 0.68, P=0.64, 95%CI: 0.13-3.47) between the TAI+ and TAI- groups. Discussion: Our retrospective cohort study found an association between TAI and reduced reproductive outcomes in women undergoing IUI for unexplained infertility. However, the meta-analysis incorporating other studies did not yield statistically significant associations. Caution is required in interpreting the relationship between thyroid autoimmunity and reproductive outcomes. Future studies should consider a broader population and a more rigorous study design to validate these findings. Clinicians dealing with women with unexplained infertility and TAI should be aware of the complexity of this field and the limitations of available evidence. [ABSTRACT FROM AUTHOR]

Up to a half of couples seeking medical assistance for infertility are diagnosed with unexplained infertility, characterized by normal ovulation, tubal patency, and semen analysis results. This condition presents a challenge in determining the optimal treatment approach. Available treatments include IUI and IVF, but guidelines vary on when to offer each. Prognosis-based management is identified as a research priority, and various prediction models have been developed to guide treatment decisions. Prognostic factors include female age, duration of subfertility, and sperm parameters, among others. Prognosis-based strategies can enhance cost-effectiveness, safety, and patient outcomes, offering less invasive options to those with good prognoses and more aggressive interventions to those with poor prognoses. However, there is a gap between research evidence and its clinical application. In this article, we discuss the application of prognosis-based management in the context of unexplained infertility, highlighting its potential to improve clinical decision-making and patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The endometrium of most unexplained infertility (UI) patients has been altered histologically. Shear wave elastography (SWE) is utilized to assess the signature of living tissue. This study aimed to explore the value of SWE in evaluating endometrial receptivity (ER) in UI patients. Methods: In total, 59 UI patients (UI group) and 52 normal control women (NC group) who received fertility consultation in our hospital were included between January 2022 and June 2023. We divided them into the late-proliferative phase of UI group (LPUI; n = 59), mid-secretory phase of UI group (MPUI; n = 41), late-proliferative phase of NC group (LPNC; n = 52), and mid-secretory phase of NC group (MPNC; n = 45). Transvaginal ultrasonography and SWE were performed during the LP and MP. Endometrial thickness (EMT), uterine artery pulsatility index (UA-PI), endometrial mean elasticity (E-mean), and mean shear wave velocities (SWV-mean) were measured. Results: There were significant differences in E-mean, SWV-mean, EMT, and UA-PI between the UI group and the NC group during both the LP and MP (p MPNC vs MPUI < 0.05, p LPNC vs LPUI < 0.05). E-mean and SWV-mean decreased with increasing EMT but increased with increasing UA-PI (p < 0.05). The most effective parameter for evaluating ER in UI patients is the E-mean (AUC = 0.89). Conclusions: UI patients exhibited thinner endometrium, increased endometrial stiffness, and poor endometrial blood perfusion. E-mean was the most effective parameter to evaluate ER in UI patients. The study preliminarily proved that SWE is a promising non-invasive tool for evaluating the condition of endometrium. Critical relevance statement: This study aimed to explore the significance of endometrial elasticity measured by SWE in evaluating patients with UI. The findings revealed a correlation between EMT, UA-PI, and E-mean. Endometrial elasticity can serve as an effective indicator for predicting ER. Key points: 1. To explore the significance of endometrial elasticity in assessing patients with UI. 2. The endometrium of UI patient exhibited thinness, stiffness, and poor blood perfusion. 3. Endometrial elasticity serves as a valuable indicator for evaluating endometrial receptivity. [ABSTRACT FROM AUTHOR]

BACKGROUND IVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy. OBJECTIVE AND RATIONALE Randomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility. SEARCH METHODS We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool. OUTCOMES Of eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81–1.74, I 2 = 42.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41–1.50, I 2 = 0.0%). WIDER IMPLICATIONS There is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility. The associated costs of interventions and the preference of couples need to be weighed in clinical decision-making. [ABSTRACT FROM AUTHOR]

BackgroundInfertility is a pressing global public health concern, affecting millions worldwide, and the diagnosis of unexplained infertility poses particular challenges. Human seminal plasma allergy, a rarely diagnosed type I hypersensitivity reaction, emerges as a potential but often overlooked contributor to female infertility. With rare reported cases globally, the condition’s low awareness and insufficient differential diagnosis may mask its actual prevalence.Case reportThis case report presents the clinical case of a 29-year-old woman with unexplained infertility who underwent two unsuccessful IVF procedures and was subsequently diagnosed with human seminal plasma allergy. The patient, known for bronchial asthma and allergic rhinitis exacerbated by inhalant allergens, exhibited eosinophilia and a history of local allergy symptoms (burning sensation, vulvar pruritus, edema, and general discomfort) as well as sneezing and nasal congestion following unprotected intercourse—symptoms compatible with human seminal plasma allergy. Molecular allergy diagnostics revealed pronounced sensitization to dust mites and Can f 5, a canine-specific allergen. A positive skin prick test using her partner’s sperm confirmed the diagnosis of human seminal plasma allergy. The patient’s medical history also includes mild endometriosis, raising questions about the interplay between allergic conditions and fertility. Treatment options such as barrier contraception, antihistamine therapy, and sperm desensitization are discussed.ConclusionHighlighting the need for increased awareness among healthcare professionals, this case emphasizes the significance of reporting and sharing clinical experiences to enhance our understanding of this rare condition. As researchers continue to accumulate relevant information, a more comprehensive understanding of human seminal plasma allergy and its potential impact on female fertility will contribute to improved diagnostic protocols and expanded treatment options. This case report contributes to the growing body of knowledge surrounding this rare allergy, serving as a reminder of possible intricate relationships between allergic conditions and reproductive health.

Objective: To evaluate the effect of follicular phase length (FPL) on pregnancy outcomes and endometrial thickness (ET) among women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination (OS-IUI) with clomiphene citrate, letrozole, or gonadotropins. Design: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial. Setting: Multicenter randomized controlled trial. Patient(s): A total of 869 couples with unexplained infertility who underwent OS-IUI treatment cycles as part of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation study. Intervention(s): FPL was evaluated as a categorical variable defined by quintiles (q1: ≤11 days, q2: 12 days, q3: 13 days, q4: 14–15 days, and q5: ≥16 days). Main outcome measure(s): Clinical pregnancy, live birth rates, and ET. Result(s): Decreasing FPL quintiles did not reduce clinical pregnancy or live birth rates in unadjusted or adjusted models with all treatment groups combined or when stratified by the ovarian stimulation medication. All FPL categories had significantly thinner ET compared with the 5th quintile (≥16 days) among women treated with clomiphene citrate or letrozole. Similar but diminished associations were observed among women who underwent ovarian stimulation with gonadotropins, but the observed differences were limited to those with FPL of 12 days or shorter when compared with FPL ≥16 days. Conclusion(s): Although shorter FPL was associated with reduced ET, it was not associated with the outcomes of clinical pregnancy or live birth in women with unexplained infertility undergoing OS-IUI in all treatment groups combined. Similar patterns existed when analyses of clinical pregnancy and live birth rates were stratified by treatment. Clinical trial registration: NCT01044862.

Male factors may be present in up to 50–70% of infertile couples and the prevalence of male infertility accounts for 20–30% of infertility cases. Understanding the mechanisms and causes behind male infertility remains a challenge, but new diagnostic tools such as DNA fragmentation might aid in cases where the routine semen analysis is insufficient. DNA fragmentation, which refers to damages or breaks of the genetic material of the spermatozoa, is considered one of the main causes of male infertility due to impaired functional capability of sperm. The aim of the present narrative review is to investigate and enlighten the potential correlation between DNA fragmentation and male infertility parameters such as the seminal profile and the reproductive outcomes. Comprehensive research in PubMed/Medline and Scopus databases was conducted and 28 studies were included in the present review. Fourteen studies provided data regarding the impact of DNA fragmentation and seminal parameters and showed a correlation of significantly lower sperm count, lower concentration, motility, and abnormal morphology with an increased DNA fragmentation index (DFI). Similarly, 15 studies provided data regarding the impact of DFI on reproductive outcomes. Two studies showed higher aneuploidy rates with higher DFI values, and seven studies showed significantly lower pregnancy rates and live birth rates with higher DFI values. Ultimately, the studies included in this review highlight, collectively, the importance of measuring sperm DFI in the assessment of male infertility. Further studies are needed to explore the effectiveness of interventions aiming to reduce DFI levels.

Aim: The objective of this document is to provide guidance to the infertility specialist, gynecologist, embryologist, and counselors on the management of sub-fertility and brief them with the recent advances in the field. These recommendations will aid the aforementioned healthcare professionals in everyday clinical decisions about appropriate and effective care of their patients with the best available evidence. Participants: Extensive deliberations, discussion, and brainstorming was done between different reproductive medicine (RM) specialists, to develop the recommendations. Evidence: A systematic review of the literature published up to June 2019 was carried out using PubMed and Cochrane Collaboration Library. International guidelines, cohort studies, case series, observational studies, and randomized controlled trials currently available in the literature were reviewed. Indian data whatever available was also reviewed. Process: Primary meetings were held with leading reproductive medicine specialists. Each topic was brainstormed on by a group of reproductive medicine experts, who then prepared the first draft of the recommendation. These recommendations then were reviewed by Dr. Jaideep Malhotra, Dr. Gouri Devi, and Dr. Madhuri Patil along with the chief co-ordinator of each consensus to finalize the final draft. Conclusions: From the literature and discussion of the available evidence, several topics were identified for which evidence is inconsistent, insufficient, or non-existing. For the benefit of couples undergoing several treatments, the working committee recommends that future research, where possible in well-designed RCTs, will help in establishing evidence for a particular practice. In the Indian context, one also needs to take into consideration facilities and options available, cost, lack of insurance coverage, experimental nature of some advanced techniques used. [ABSTRACT FROM AUTHOR]

Infertility is a complex condition affecting millions of couples worldwide. The current definition of infertility, based on clinical criteria, fails to account for the molecular and cellular changes that may occur during the development of infertility. Recent advancements in sequencing technology and single-cell analysis offer new opportunities to gain a deeper understanding of these changes. The endometrium has a potential role in infertility and has been extensively studied to identify gene expression profiles associated with (impaired) endometrial receptivity. However, limited overlap among studies hampers the identification of relevant downstream pathways that could play a role in the development of endometrial-related infertility. To address these challenges, we propose sequencing the endometrial transcriptome of healthy and infertile women at the single-cell level to consistently identify molecular signatures. Establishing consensus on physiological patterns in endometrial samples can aid in identifying deviations in infertile patients. A similar strategy has been used with great success in cancer research. However, large collaborative initiatives, international uniform protocols of sample collection and processing are crucial to ensure reliability and reproducibility. Overall, the proposed approach holds promise for an objective and accurate classification of endometrial-based infertility and has the potential to improve diagnosis and treatment outcomes. [ABSTRACT FROM AUTHOR]

Endometriosis, a systemic ailment, profoundly affects various aspects of life, often eluding detection for over a decade. This leads to enduring issues such as chronic pain, infertility, emotional strain, and potential organ dysfunction. The prolonged absence of diagnosis can contribute to unexplained obstetric challenges and fertility issues, necessitating costly and emotionally taxing treatments. While biopsy remains the gold standard for diagnosis, emerging noninvasive screening methods are gaining prominence. These tests can indicate endometriosis in cases of unexplained infertility, offering valuable insights to patients and physicians managing both obstetric and non-obstetric conditions. In a retrospective cross-sectional study involving 215 patients aged 25 to 45 with unexplained infertility, diagnostic laparoscopy was performed after unsuccessful reproductive technology attempts. Pathology results revealed tissue abnormalities in 98.6% of patients, with 90.7% showing endometriosis, confirmed by the presence of endometrial-like glands and stroma. The study underscores the potential role of endometriosis in unexplained infertility cases. Although the study acknowledges selection bias, a higher than previously reported prevalence suggests evaluating endometriosis in patients who have not responded to previous reproductive interventions may be justified. Early detection holds significance due to associations with ovarian cancer, prolonged fertility drug use, pregnancy complications, and elevated post-delivery stroke risk. [ABSTRACT FROM AUTHOR]

Infertility of no obvious cause or after correction of the factor identified as responsible for infertility. Unexplained infertility is diagnosed when all of the standard elements of the infertility evaluation yield normal results. The incidence of unexplained infertility ranges from 10% to as high as 30% among infertile populations depending on diagnostic criteria. Patients admitted in hospital with H/O infertility was evaluated by taking a detail history, performed a clinical examination and relevant investigation. After obtaining anesthesia fitness, suitable patient was posted for hysterolaparoscopy procedure under general anesthesia & intra op findings was documented. The majority of the study subjects that is 20 (40%) were in the age group of 26-30 yrs. 17 (34%) were in the age group of above 30 years. There were 13 (26%) in the age group of 21-25 years. The youngest patient in the series was 21 years. The oldest patient in the series was 36 years. These were no patients over the age of 36 years. This may not exactly reflect the decrease in infertility at a latter age but may be the reluctance of the women in our society to seek treatment for infertility over 36years. Out of 50 patients majority were 6-10years of duration that is 54%, 1-5 years duration 42%, more than 10 years 4%. [ABSTRACT FROM AUTHOR]

Unexplained subfertility (UEI) describes a couple whose standard subfertility workout consider acceptable but unable to conceived. This retrospective study was conducted in the Advanced Reproductive Centre, UKM Hospital, Kuala Lumpur, from January 2016 to December 2019. The data of 268 UEI couples were obtained from the clinical database. Women aged 21–45 years old was included and further divided into four groups according to the female partner's age and subfertility duration: group A (age <35 years and subfertility <2 years), group B (age <35 years and subfertility >2 years), group C (age >35 years and subfertility <2 years), and group D (age >35 years and subfertility <2 years). All statistical analyses were performed using SPSS 22.0 for Windows. A total of 255 cases were included in this study. The mean age of the women was 32.9 ± 4.04 years, and the mean subfertility duration was 5.04 ± 2.9 years. A total of 51 (20 %) cases underwent timed sexual intercourse, 147 (57.6 %) cases had intrauterine insemination (IUI), whereas 57 (22.4 %) cases opted for in vitro fertilization (IVF). A total of 204 cases underwent active management (IUI/IVF), which showed a significant difference (p<0.05). Out of eight clinical pregnancies, half of them were from group B. Active management in younger women with a shorter subfertility duration revealed a better pregnancy outcome. Otherwise, individualized treatment should be considered in selecting a suitable treatment plan. [ABSTRACT FROM AUTHOR]

Abstract Background Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results. Aims This review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines. Methods The primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected. Discussion/conclusion This review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women 38 years. Patients should be appropriately counselled to enable informed decision making.

Abstract Background This study aimed to investigate the prescription of traditional herbal medicines for the treatment of unexplained female infertility in Korea. By analyzing the relationships among the prescriptions and between the prescriptions and treatment outcomes, we aimed to confirm the utilization of standardized prescriptions and the effectiveness of this standardization. Methods The data were derived from the “support projects” of the local government for infertile women to receive Korean medical treatments. The presciption data of 453 participants from 2017 to 2018 were analyzed. Data preprocessing, frequency analysis, and network analysis were conducted. For network analysis, the characteristics of the herbal medicine prescriptions were used to calculate the degree centrality, closeness centrality and eigenvector centrality. Modularity clustering was also performed for cluster analysis. Results Fifty different prescriptions were used, among which only 22 were used for participants who became pregnant. The recommended standard prescriptions for support projects were used frequently. “BaeranChacksangBang” showed the highest level of in-degree centrality. Among the prescriptions for participants who became pregnant, “JogyeongJongokTang” and “BaeranChacksangBang” were the most influential nodes. “BaeranChacksangBang”, “AnjeonYicheonTang”, “YukLinZu” and “JogyeongJongokTang” had high closeness centrality among the prescriptions for participants who became pregnant. Clustering analysis of the prescriptions for participants who became pregnant revealed that the prescriptions showed the best modularity when divided into five groups. Conclusions These findings depict the utilization of Korean herbal medicine in the real world and the dynamics underlying the herbal medicine prescription patterns for infertile women.

Objective: To determine if moderate physical activity is associated with live birth rates in women with unexplained infertility and obesity. Design: Secondary analysis of the Improving Reproductive Fitness through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility trial. Setting: US fertility centers, 2015–2019. Patient(s): A total of 379 women participated in Improving Reproductive Fitness through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility trial, a lifestyle modification program with increased physical activity (phase I, 16 weeks) and up to three cycles of clomiphene citrate treatment and intrauterine insemination (phase II). Intervention(s): Participants were instructed to add 500 steps/day weekly until a maximum of 10,000 steps/day was reached and maintained. Participants were stratified as active (top third, N = 125) and less active (lower third, N = 125) on the basis of the average number of steps per day recorded using a FitBit activity tracker. Main Outcome Measure(s): Live birth rate. Result(s): Active participants were more physically active at the time of enrollment than less active participants (average baseline steps per day, 8,708 [7,079–10,000] vs. 4,695 [3,844–5,811]; P ≤ 0.001) and were more likely to reach 10,000 steps/day than less active participants (average steps per day, 10,526 [9,481–11,810] vs. 6,442 [4,644–7,747]; P ≤ 0.001), although both groups increased their average steps per day by a similar amount (1,818 vs.1,747; P = 0.57). There was no difference in live birth rates (24/125 [19.2%] vs. 25/125 [20%]; P = 0.87) between active and less active participants nor were there differences in clinical pregnancy rates (P = 0.45) or miscarriage rates (P = 0.49) between the two groups. Conclusion(s): Active participants were more likely to achieve the physical activity goal, although this was not associated with benefit or harm with respect to live birth. Clinical Trial Registration Number: ClinicalTrials.gov (NCT02432209), first posted: May 4, 2015.

Abstract Purpose This paper was mainly conducted to investigate the effect of chronic endometritis (CE) on the clinical outcome of patients with unexplained infertility. Materials and methods 145 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. Results There 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

Background: Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results. Aims: This review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines. Methods: The primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected. Discussion/conclusion: This review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women < 38 years, with good prognosis, and IVF could be offered first to those > 38 years. Patients should be appropriately counselled to enable informed decision making. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the prescription of traditional herbal medicines for the treatment of unexplained female infertility in Korea. By analyzing the relationships among the prescriptions and between the prescriptions and treatment outcomes, we aimed to confirm the utilization of standardized prescriptions and the effectiveness of this standardization. Methods: The data were derived from the "support projects" of the local government for infertile women to receive Korean medical treatments. The presciption data of 453 participants from 2017 to 2018 were analyzed. Data preprocessing, frequency analysis, and network analysis were conducted. For network analysis, the characteristics of the herbal medicine prescriptions were used to calculate the degree centrality, closeness centrality and eigenvector centrality. Modularity clustering was also performed for cluster analysis. Results: Fifty different prescriptions were used, among which only 22 were used for participants who became pregnant. The recommended standard prescriptions for support projects were used frequently. "BaeranChacksangBang" showed the highest level of in-degree centrality. Among the prescriptions for participants who became pregnant, "JogyeongJongokTang" and "BaeranChacksangBang" were the most influential nodes. "BaeranChacksangBang", "AnjeonYicheonTang", "YukLinZu" and "JogyeongJongokTang" had high closeness centrality among the prescriptions for participants who became pregnant. Clustering analysis of the prescriptions for participants who became pregnant revealed that the prescriptions showed the best modularity when divided into five groups. Conclusions: These findings depict the utilization of Korean herbal medicine in the real world and the dynamics underlying the herbal medicine prescription patterns for infertile women. [ABSTRACT FROM AUTHOR]

Background: There is ongoing research to find an optimum modality to predict male fertility potential. Aims: To compare the semen parameters, sperm DNA damage and seminal metal levels of Zinc, Lead and Aluminium among the male partners of couples with unexplained infertility and men with proven fertility. Settings and Design: Prospective case-control study at a tertiary level teaching hospital. Materials and Methods: One hundred male partners of couples with unexplained subfertility and 50 men with proven fertility were included in the study. Male partners of unexplained infertility couples and fertile men were compared for their semen parameters, sperm DNA Fragmentation Index (DFI) and seminal metal levels in semen. Statistical Analysis Used: Chi-square test, Student's t-test, sensitivity and specificity analysis, binomial logistic regression analysis. Results: Fertile men had statistically significantly higher mean progressive sperm motility than male partners of unexplained infertility (53.12 ± 9.89% vs. 44.81 ± 19.47%, P = 0.005). Semen volume and sperm concentration were comparable among the cases and control population. The mean sperm DFI was significantly lower among fertile men (10.83 ± 6.28 vs. 21.38 ± 10.28, P < 0.0001). Plotting the receiver-operating characteristic curve the threshold for discrimination was calculated to be 18% DFI. The sensitivity specificity and overall accuracy were 43%, 84% and 56.67%, respectively when the DFI cut-off was set at 18%. Zinc concentration in the semen had a strong positive correlation (Point Biserial correlation coefficient = 0.831) with fertility, whereas lead and aluminium had a moderate negative correlation. Conclusion: Conventional semen analysis had limited differentiating ability for unexplained infertility. The sperm DFI may be employed for explanatory purposes among couples with unexplained subfertility. A lower discriminatory threshold of DFI (18%) has better overall accuracy as opposed to a 30% cutpoint for unexplained subfertility. Among metals, Zinc was strongly correlated with fertility status. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the recommended management for couples presenting with unexplained infertility (UI), based on the best available evidence in the literature? SUMMARY ANSWER The evidence-based guideline on UI makes 52 recommendations on the definition, diagnosis, and treatment of UI. WHAT IS KNOWN ALREADY UI is diagnosed in the absence of any abnormalities of the female and male reproductive systems after 'standard' investigations. However, a consensual standardization of the diagnostic work-up is still lacking. The management of UI is traditionally empirical. The efficacy, safety, costs, and risks of treatment options have not been subjected to robust evaluation. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for ESHRE guidelines. Following formulation of key questions by a group of experts, literature searches, and assessments were undertaken. Papers written in English and published up to 24 October 2022 were evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the available evidence, recommendations were formulated and discussed until consensus was reached within the guideline development group (GDG). Following stakeholder review of an initial draft, the final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help clinicians provide the best care for couples with UI. As UI is a diagnosis of exclusion, the guideline outlined the basic diagnostic procedures that couples should/could undergo during an infertility work-up, and explored the need for additional tests. The first-line treatment for couples with UI was deemed to be IUI in combination with ovarian stimulation. The place of additional and alternative options for treatment of UI was also evaluated. The GDG made 52 recommendations on diagnosis and treatment for couples with UI. The GDG formulated 40 evidence-based recommendations—of which 29 were formulated as strong recommendations and 11 as weak—10 good practice points and two research only recommendations. Of the evidence-based recommendations, none were supported by high-quality evidence, one by moderate-quality evidence, nine by low-quality evidence, and 31 by very low-quality evidence. To support future research in UI, a list of research recommendations was provided. LIMITATIONS, REASONS FOR CAUTION Most additional diagnostic tests and interventions in couples with UI have not been subjected to robust evaluation. For a large proportion of these tests and treatments, evidence was very limited and of very low quality. More evidence is required, and the results of future studies may result in the current recommendations being revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in the care of couples with UI, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field. The full guideline and a patient leaflet are available in www.eshre.eu/guideline/UI. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed by ESHRE, who funded the guideline meetings, literature searches, and dissemination of the guideline in collaboration with the Monash University led Australian NHMRC Centre of Research Excellence in Women's Health in Reproductive Life (CREWHIRL). The guideline group members did not receive any financial incentives; all work was provided voluntarily. D.R. reports honoraria from IBSA and Novo Nordisk. B.A. reports speakers' fees from Merck, Gedeon Richter, Organon and Intas Pharma; is part of the advisory board for Organon Turkey and president of the Turkish Society of Reproductive Medicine. S.B. reports speakers' fees from Merck, Organon, Ferring, the Ostetric and Gynaecological Society of Singapore and the Taiwanese Society for Reproductive Medicine; editor and contributing author, Reproductive Medicine for the MRCOG, Cambridge University Press; is part of the METAFOR and CAPE trials data monitoring committee. E.B. reports research grants from Roche diagnostics, Gedeon Richter and IBSA; speaker's fees from Merck, Ferring, MSD, Roche Diagnostics, Gedeon Richter, IBSA; E.B. is also a part of an Advisory Board of Ferring Pharmaceuticals, MSD, Roche Diagnostics, IBSA, Merck, Abbott and Gedeon Richter. M.M. reports consulting fees from Mojo Fertility Ltd. R.J.N. reports research grant from Australian National Health and Medical Research Council (NHMRC); consulting fees from Flinders Fertility Adelaide, VinMec Hospital Hanoi Vietnam; speaker's fees from Merck Australia, Cadilla Pharma India, Ferring Australia; chair clinical advisory committee Westmead Fertility and research institute MyDuc Hospital Vietnam. T.P. is a part of the Research Council of Finland and reports research grants from Roche Diagnostics, Novo Nordics and Sigrid Juselius foundation; consulting fees from Roche Diagnostics and organon; speaker's fees from Gedeon Richter, Roche, Exeltis, Organon, Ferring and Korento patient organization; is a part of NFOG, AE-PCOS society and several Finnish associations. S.S.R. reports research grants from Roche Diagnostics, Organon, Theramex; consulting fees from Ferring Pharmaceuticals, MSD and Organon; speaker's fees from Ferring Pharmaceuticals, MSD/Organon, Besins, Theramex, Gedeon Richter; travel support from Gedeon Richter; S.S.R. is part of the Data Safety Monitoring Board of TTRANSPORT and deputy of the ESHRE Special Interest Group on Safety and Quality in ART; stock or stock options from IVI Lisboa, Clínica de Reprodução assistida Lda; equipment/medical writing/gifts from Roche Diagnostics and Ferring Pharmaceuticals. S.K.S. reports speakers' fees from Merck, Ferring, MSD, Pharmasure. HRV reports consulting and travel fees from Ferring Pharmaceuticals. The other authors have nothing to disclose. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.) [ABSTRACT FROM AUTHOR]

Background: Infertility is a global public health issue affecting couples. Trace metals have been implicated in effective reproductive functions in males but less studied in females. Objective: To compare the serum levels of copper(Cu), zinc (Zn), selenium (Se) and copper/zinc ratio in women with unexplained infertility and fertile women. Subjects and Methods: This was a cross-sectional analytical study that compared 75 consenting women who had unexplained infertility with 74 fertile women that were controls. Both groups were seen within 1 year of delivery and were recruited from the family planning unit, at the University College Hospital, Ibadan. Data were obtained through a semi-structured questionnaire, after which 10 mL of venous blood was collected. Analysis of selected trace elements were done by atomic absorption spectrophotometry. IBM SPSS version 23 was utilized for data analysis and the levels of statistical significance was set at <0.05. Results: The mean (± SD) serum concentrations of Cu (93.11 ± 16.55 μg/dL), Zn (72.04 ± 15.03 μg/dL) and Se (28.28 ± 8.33 μg/dL) amongst the women with unexplained infertility were lower when compared to the control group (all with P < 0.001). The serum Cu/Zn ratio was higher among the fertile women, though not statistically significant (P < 0.62). Age of <35 years was associated with normal serum levels of Cu (P < 0.01), while women with normal body mass index had low serum concentrations of Cu (P = 0.04), amongst the fertile group. Conclusion: Serum copper, zinc and selenium concentrations are significantly lower in women with unexplained infertility, therefore diets or supplements containing these trace elements may be helpful in their management. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to investigate whether the number of dominant follicles formed in IUI with OS affects pregnancy outcomes in couples with unexplained infertility. Material and Method: 217 couples aged 24-39 years with unexplained infertility and treated with IUI byway of ovarian stimulation participated in our study. The patients were divided into 2 groups of which the first included the clinically pregnant and the second did not, and were compared in terms of age, monofollicle and bifollicle development, infertility duration, treatment initiation day, hcg day, leading follicle diameter, endometrial thickness, number of dominant follicles and treatment type. Results: Of the 217 patients who underwent IUI for unexplained infertility, no significant difference was found between the groups with and without clinical pregnancy in terms of the number of dominant follicles (p=0.73). There was a positive but low correlation between endometrial thickness and treatment success (Spearman's correlation coefficient value = 0.14, p=0.03). The receiver operating characteristic curve analysis revealed that the optimal cut-off value for endometrial thickness to predict pregnancy success was 9.5 mm (55.0% sensitivity, 65.0% specificity). Conclusions: As a result, we suggest that gonadotropins are not superior to oral agents in terms of clinical pregnancy rates in unexplained infertility, therefore treatment should commence with less invasive and less costly oral agents. Furthermore, we think that the number of dominant follicles (monofollicles or bifollicles) created by ovarian stimulation does not affect clinical pregnancy success, but endometrial thickness is closely related to pregnancy rates and deserves attention. [ABSTRACT FROM AUTHOR]

To explore the association of leukemia inhibitory factor receptor (LIFR) gene variant rs3099124, ovarian steroids, and leukemia inhibitory factor with unexplained infertility in Pakistani females. A case–control investigation in which eighty-one (81) females with unexplained infertility and one hundred and sixty-two (162) fertile counterparts (age and body mass index compared) were recruited between October 2016 and 2018. Ten milliliters of venous blood was collected from all participants. "Genomic DNA" was taken out from lymphocytes in peripheral blood samples. "Tetra Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR)" was constructed through software "Primer-I". Amplification was carried out by "T-ARMS-PCR" followed by subsequent sequencing for confirmation and extensive consonance. Estradiol, Progesterone and Leukemia Inhibitory Factor (LIF) were measured in serum by ELISA. Statistically significant difference was noticed in genotype frequency in "LIFR-gene variant; rs3099124" (χ2 = 28.222, P value < 0.01) between research participants. Although, rs "3099124" "AA" (OR = 0.000; 95%CI = 0–0) and "GA" genotypes (OR = 0.525; 95%CI = 0.226–1.22) showed non-significant safety/protection against unexplained infertility yet minor/risk allele "A" frequency was greater in women with unexplained infertility suggesting a possible explanation of implantation failure. LIF concentration varied between fertile and infertile groups (χ2 = 9.857, P < 0.05) revealing significant threat of unexplained infertility in women with decreased LIF concentration (OR = 2.316, 95%CI = 1.214–4.416). Progesterone was significantly related to unexplained infertility in both study groups (χ2 = 20.347, P < 0.05). High progesterone reduced the possibility of unexplained infertility (OR = 0.306; 95% CI = 0.166–0.567). LIFR gene variation (rs3099124) and reduced LIF secretion may cause implantation failure in women with unexplained infertility. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The primary objective of our study was to compare the endometrial microbiota profiles of women with unexplained infertility and fertile women. STUDY DESIGN: In this case control study a total of 15 patients with unexplained infertility and 15 patients who had a live birth in the last two years with proven fertility were recruited. Endometrial samples were collected and analyzed through next-generation sequencing of the bacteria-specific 16S ribosome gene. RESULTS: Lactobacillus species represented the majority of the microbiome profile in both groups. The median percentage of the endometrial Lactobacillus between infertile patients and fertile patients was not statistically significant (p=0.9). Groups were divided into two categories: Lactobasillus dominant (Lactobacillus spp.> 90%, LD) and Non-Lactobacillus dominant (NLD). Lactobacillus dominance was detected in six of nine patients (66.7%) in the study group and four of nine patients (44.5%) in the control group, and no significant difference was observed between them (p=0.64). CONCLUSION: According to our study results, no significant difference was observed between the endometrial microbiota profile of infertile and fertile patients. Further studies with larger sample sizes are needed to characterize the endometrial microbiota and its impact on reproduction. [ABSTRACT FROM AUTHOR]

Aim: Hypogonadotropic hypogonadism (HH) is a rare clinical condition resulting from gonadal insufficiency due to low pituitary gonadotropin levels. Since ovulation occurs rarely in these patients, the probability of spontaneous pregnancy is very low. The study aimed to evaluate the in vitro fertilization (IVF) treatment outcomes in patients with HH and to compare these results with that of patients with unexplained infertility (UI) who underwent IVF treatment. Material and Methods: In this study, 36 cycles of 28 HH patients who underwent IVF treatment and 72 cycles of 68 patients who underwent IVF treatment for UI were included. Demographic data, ovarian hyperstimulation and cycle outcomes, clinical pregnancy rates, and predictive factors for clinical pregnancy were evaluated retrospectively, and the two groups were compared. Results: In the HH group, clinical pregnancy, and live birth rates per cycle after IVF were significantly higher compared with the UI group (n=16, 44.4% vs. n=17, 23.6%, p=0.027; and n=14, 38.9% vs. n=14, 19.4%; p=0.030, respectively). Although the number of antral follicles (p=0.001) and retrieved oocytes (p=0.042) were significantly higher in the UI group, the number of mature oocytes and grade I-II embryos were similar in the HH and UI groups. The total gonadotropin dose used and duration of stimulation in the HH group were significantly higher than in the UI group (both p=0.001). Conclusion: HH patients responded well to IVF treatment and had better IVF outcomes compared to women who underwent IVF for UI. No prognostic factor that affected pregnancy success in HH patients was detected.

Aim: The aim of this study was to determine the effect of paternal age on miscarriage rates in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment cycles. Material and Methods: Patients were classified into two groups. The study group consisted of the patients whose pregnancy resulted in a miscarriage (n=73) and a control group in which the patients had a live singleton birth (n=256). Demographic characteristics, treatment indications, duration of infertility, menstruation day 3 follicle stimulating hormone, estradiol, luteinizing hormone, total antral follicle count, anti-Mullerian hormone levels and controlled ovarian stimulation parameters, day of trigger, estradiol and progesterone levels on the day of trigger, the total number of oocytes retrieved, the number of mature oocytes, the number and quality of the embryo, endometrial thickness on the day of trigger, oocyte pick up and embryo transfer, the distance of embryo-fundus and the day of embryo transfer were recorded. Results: Totally 329 women were included in the present study. The number of patients with the diagnosis of unexplained infertility was statistically significantly higher in the study group than in the control group (p=0.020). Maternal age was found statistically significantly higher in the study group than in the control group (p=0.025). When maternal age increased by 1 unit, the risk of miscarriage increased by 8.7% and those with unexplained infertility had a 75.6% higher risk of miscarriage than those without unexplained infertility. Conclusion: Paternal age was not associated with miscarriage whereas maternal age and unexplained infertility had a positive correlation with miscarriage rate.

Background: Infertility is becoming a bigger problem in society. Since hysteroscopy, the gold standard diagnostic method, is an intrusive procedure, a study that could get around its drawbacks was necessary. Hysteroscopy might be replaced by 3D transvaginal sonography [3D TVS], which simultaneously registers all three image planes and non-invasively visualizes uterine morphology.Aim of the work: Comparison between the diagnostic accuracy of 3D transvaginal ultrasound and diagnostic hysteroscopy in the evaluation of women with unexplained infertility.Patients and Methods: This comparative interventional study was conducted in the infertility clinic of Al-Azhar Cairo University Hospitals [Sayed Galal and El Hussein Hospitals] between February 2021 and February 2022. A total of one hundred women with unexplained infertility were enrolled and subjected to both 3D transvaginal sonography and diagnostic hysteroscopy.Results: Abnormalities that were detected by vaginal ultrasonography were intrauterine adhesions, which were detected in 20 [20%] cases; fibroid was found in 28 [28% cases]; intrauterine polyps were found in 25 [25% cases]; and septum was detected in 3 [3%] cases. By hysteroscopy, which is the gold standard in investigating the uterine cavity, abnormal findings were found in 90 cases, representing 90% of cases, whereas 10 [10%] cases were free.Conclusion: Three-dimensional transvaginal sonography is increasingly being used as a standard procedure to examine infertile women since it is excellent at detecting uterine cavity defects. Transvaginal sonography findings should be confirmed by hysteroscopy, the gold standard in uterine cavity investigation, as well as when transvaginal sonography produces conflicting results.

Endometriosis is a prevalent condition that affects millions of individuals globally, leading to various symptoms and significant disruptions to their quality of life. However, the diagnosis of endometriosis often encounters delays, emphasizing the pressing need for non-invasive screening. This retrospective cross-sectional study aimed to evaluate the utility of the Endometriosis Risk Advisor (EndoRA) mobile application in screening for endometriosis in patients with chronic pelvic pain and/or unexplained infertility. The study consisted of 293 patients who met specific criteria: they were English-speaking individuals with chronic pelvic pain and/or unexplained infertility, owned smartphones, and had no prior diagnosis of endometriosis. The results demonstrated that the EndoRA score exhibited a high sensitivity of 93.1% but a low specificity of 5.9% in detecting endometriosis. The positive predictive value was 94.1%, while the negative predictive value was 5.0%. Although the study had limitations and potential selection bias, its findings suggest that EndoRA can serve as a valuable screening tool for high-risk individuals, enabling them to identify themselves as being at an increased risk for endometriosis. EndoRA's non-invasive nature, free access, and easy accessibility have the potential to streamline evaluation and treatment processes, thereby empowering individuals to seek timely care and ultimately improving patient outcomes and overall well-being. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the correlation between hydrogen peroxide (H2O2), small ubiquitin-like modifier molecules (SUMO), and pregnancy outcomes in couples with unexplained infertility (UI) undergoing intrauterine insemination (IUI) treatment. We prospectively collected semen samples from 56 couples with UI and divided the spermatozoa into motile and immotile fractions by density gradient centrifugation (DSC). Immunofluorescence staining was used to examine the immunostaining and localization of nuclear pore complex (NPC), SUMO1, and SUMO2/3 in spermatozoa. We detected H2O2 levels by chemiluminescence methods. We found that H2O2 levels correlated with NPC (neck) (r = 0.400) and NPC (tail) (r = 0.473) in motile sperm fractions. In immotile fractions, H2O2 positively correlated with NPC (tail) (r = 0.431) and SUMO1 (neck) (r = 0.282). Furthermore, the positive NPC (tail) group had a significantly lower live birth rate than the negative NPC group (17.9% = 5/28 vs. 42.9% = 12/28). In conclusion, H2O2 positively correlated with SUMO1 (neck) and NPC (tail) in human spermatozoa. The DSC may partially eliminate defective spermatozoa (positive NPC staining); however, if defective spermatozoa remain in the motile fraction, this scenario is associated with a low live birth rate following IUI treatment. [ABSTRACT FROM AUTHOR]