Semen Washing and Intrauterine Insemination for Reducing the Risk of Human Immunodeficiency Virus Transmission in Serodiscordant Couples: A Cross-sectional Study.

Background: Antiretroviral therapy has helped human immunodeficiency virus (HIV)-infected people live an enhanced quality of life and attempt for a pregnancy, without placing their partner at risk. Although periconceptional pre-exposure prophylaxis for the uninfected partner and consistent antiretroviral therapy for the HIV-infected partner are important to prevent HIV transmission, semen washing could be a great option to further reduce the semen viral load. Aim: The aim of this study were as follows: to determine if semen washing with intrauterine insemination provides an added safety net to HIV-serodiscordant couples when the male partner is HIV-infected and virally suppressed and to determine if the U = U concept (undetectable = untransmittable) holds true in virally suppressed HIV-infected males. Settings and Design: This was an observational study conducted in seropositive HIV men under treatment with highly active antiretroviral therapy (HAART) in collaboration with Metropolis Laboratory, a CAP recognised private Healthcare Laboratory in Mumbai, India. Materials and Methods: Blood and semen samples were collected from a total of 110 adult HIV-1-infected males virally suppressed on HAART. These samples were processed to assess the viral load in plasma as well as raw and processed semen fractions. Statistical Analysis Used: Descriptive statistics were used to analyse the data. Results: Only men with plasma viral loads < 1000 copies were selected in our study. Out of the 110 HIV-infected individuals, 102 (92.73%) patients had undetectable (<20 copies/ml) plasma viral load while 8 (7.27%) patients had a detectable (>20 copies/ml) viral load, who were excluded from the study. In the virally suppressed 102 men, the raw semen samples of 100 men showed an undetectable viral load, while 2 samples showed detectable contamination, even though their plasma samples from the blood showed a viral load of <20 copies/ml. The semen was then separated into the sperm and the seminal plasma samples. The seminal plasma had <20 copies/ml in 95 samples (93.14%) but a detectable viral load in 7 (6.86%) samples. After subjecting all the 102 processed (post-wash) sperm samples to quantitative analysis, an undetectable viral load of <20 copies/ml was found in all the samples. Thus, the raw sample (prewashed),seminal plasma and processed (postwash) samples were evaluated. The post-wash sperm sample showing zero contamination was frozen for intrauterine insemination (IUI) in the uninfected female partner. Conclusions: Semen washing with IUI should be advocated as a safe, efficacious way to increase the safety net and to further reduce the minimal risk of HIV transmission in serodiscordant couples in addition to the U = U concept.

Updates to Male Infertility: AUA/ASRM Guideline (2024).

PURPOSE: In 2023 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2020 publication of this Guideline. The resulting 2024 Guideline Amendment addresses updated recommendations to provide guidance on the appropriate evaluation and management of the male partner in an infertile couple. MATERIALS AND METHODS: In 2023, the Male Infertility Guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines. An updated literature search identified 4093 new abstracts. Following initial abstract screening, 125 eligible study abstracts met inclusion criteria. On data extraction, 22 studies of interest were included in the final evidence base to inform the Guideline amendment. RESULTS: The Panel developed evidence- and consensus-based statements based on an updated review to provide guidance on evaluation and management of male infertility. These updates are detailed herein. CONCLUSIONS: This update provides several new insights, including revised thresholds for Y-chromosome microdeletion testing, indications for pelvic MRI imaging in infertile males, and guidance regarding the use of testicular sperm in nonazoospermic males. This Guideline will require further review as the diagnostic and treatment options in this space continue to evolve.

Anti-Müllerian hormone does not predict cumulative pregnancy rate in non-infertile women following four IUI cycles with donor sperm.

PURPOSE: To evaluate the predictive value of serum AMH for clinical pregnancy in non-infertile population undergoing intrauterine insemination with donor sperm (ds-IUI). METHODS: This multicenter prospective study (ClinicalTrials.gov ID: NCT06263192) recruited all non-infertile women undergoing ds-IUI from June 2020 to December 2022 in three different fertility clinics in Spain and Chile. Indications for ds-IUI included severe oligoasthenoteratozoospermia, female partner, or single status. Clinical pregnancy rates were compared between women with AMH ≥ 1.1 and < 1.1 ng/mL. The main outcome measure was the cumulative clinical pregnancy rate after up to 4 ds-IUI cycles. RESULTS: A total of 458 ds-IUI cycles were performed among 245 patients, of whom 108 (44.08%) achieved clinical pregnancy within 4 cycles, 60.2% of these occurring in the first attempt and 84.2% after two attempts. We found no significant differences in AMH levels or other parameters (such as age, BMI, FSH, AFC) between women who became pregnant and those who did not. Cumulative pregnancy rates and logistic regression analysis revealed that AMH ≥ 1.1 ng/mL was not predictive of ds-IUI success. While a high positive correlation was observed between AFC and AMH (r = 0.67, p < 0.001), ROC curve analyses indicated that neither of these ovarian reserve markers accurately forecasts cumulative ds-IUI outcomes in non-infertile women. CONCLUSIONS: The findings of this multicenter study suggest that AMH is not a reliable predictor of pregnancy in non-infertile women undergoing ds-IUI. Even women with low AMH levels can achieve successful pregnancy outcomes, supporting the notion that diminished ovarian reserve should not restrict access to ds-IUI treatments in eligible non-infertile women.

Luteal phase support with oral progesterone improves live birth rate in intrauterine insemination cycles using letrozole.

RESEARCH QUESTION: Does luteal phase support (LPS) with oral progesterone improve the live birth rate (LBR) in patients undergoing intrauterine insemination (IUI) cycles with letrozole? DESIGN: This retrospective cohort study included 1199 IUI cycles with letrozole between January 2017 and December 2021. A nearest neighbour random matching approach was employed to pair the LPS group and the control group in a 1:2 ratio. Eight variables were chosen for matching in the propensity score matching (PSM) model: age; body mass index; duration of infertility; cause(s) of infertility; antral follicle count; basal concentration of FSH; rank of IUI attempts; and leading follicle size. LBR was selected as the primary outcome. RESULTS: In total, 427 LPS cycles were matched with 772 non-LPS (control) cycles after PSM. The LBR was significantly higher in the LPS group compared with the control group (19.7% versus 14.5%; P = 0.0255). The clinical pregnancy rate (23.2% versus 17.6%; P = 0.0245) and ongoing pregnancy rate (20.6% versus 15.8%; P = 0.0437) were also significantly higher in the LPS group. The biochemical pregnancy rate, ectopic pregnancy rate and miscarriage rate were similar in the two groups (P > 0.05). The intergroup comparison revealed no significant variances in terms of gestational age, mode of delivery, ectopic pregnancy rate or abortion rate. Furthermore, there were no significant differences in birth weight or birth length between the two groups. CONCLUSIONS: Luteal support with oral progesterone significantly improved the LBR in IUI cycles with letrozole, but did not affect neonatal outcomes.

The impact of clomiphene citrate on the endometrium in comparison to gonadotropins in intrauterine insemination cycles: is it thinner and does it matter?

Objective: To determine whether endometrial thickness (EMT) differs between i) clomiphene citrate (CC) and gonadotropin (Gn) utilizing patients as their own controls, and ii) patients who conceived with CC and those who did not. Furthermore, to investigate the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles. Methods: Retrospective study. Three sets of analyses were conducted separately for the purpose of this study. In analysis 1, we included all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307), to compare EMT differences between CC/IUI and Gn/IUI, utilizing women as their own controls. In analysis 2, we included all CC/IUI cycles (CC2, n=686) from women who eventually conceived with CC during the same study period, to evaluate EMT differences between patients who conceived with CC (CC2) and those who did not (CC1). In analysis 3, pregnancy outcomes among different EMT quartiles were evaluated in CC/IUI and Gn/IUI cycles, separately, to investigate the potential association between EMT and pregnancy outcomes. Results: In analysis 1, when CC1 was compared to Gn1 cycles, EMT was noted to be significantly thinner [Median (IQR): 6.8 (5.5-8.0) vs. 8.3 (7.0-10.0) mm, p<0.001]. Within-patient, CC1 compared to Gn1 EMT was on average 1.7mm thinner. Generalized linear mixed models, adjusted for confounders, revealed similar results (coefficient: 1.69, 95% CI: 1.52-1.85, CC1 as ref.). In analysis 2, CC1 was compared to CC2 EMT, the former being thinner both before [Median (IQR): 6.8 (5.5-8.0) vs. 7.2 (6.0-8.9) mm, p<0.001] and after adjustment (coefficient: 0.59, 95%CI: 0.34-0.85, CC1 as ref.). In analysis 3, clinical pregnancy rates (CPRs) and ongoing pregnancy rates (OPRs) improved as EMT quartiles increased (Q1 to Q4) among CC cycles (p<0.001, p<0.001, respectively), while no such trend was observed among Gn cycles (p=0.94, p=0.68, respectively). Generalized estimating equations models, adjusted for confounders, suggested that EMT was positively associated with CPR and OPR in CC cycles, but not in Gn cycles. Conclusions: Within-patient, CC generally resulted in thinner EMT compared to Gn. Thinner endometrium was associated with decreased OPR in CC cycles, while no such association was detected in Gn cycles.

Effect of prematurely elevated late follicular progesterone on pregnancy outcomes following ovarian stimulation-intrauterine insemination for unexplained infertility: secondary analysis of the AMIGOS trial.

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.

Development of a machine learning-based prediction model for clinical pregnancy of intrauterine insemination in a large Chinese population.

PURPOSE: This study aimed to evaluate the effectiveness of a random forest (RF) model in predicting clinical pregnancy outcomes from intrauterine insemination (IUI) and identifying significant factors affecting IUI pregnancy in a large Chinese population. METHODS: RESULTS: A total of 11 variables, including eight from female (age, body mass index, duration of infertility, prior miscarriage, and spontaneous abortion), hormone levels (anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone), and three from male (smoking, semen volume, and sperm concentration), were identified as the significant variables associated with IUI clinical pregnancy in our Chinese dataset. The RF-based prediction model presents an area under the receiver operating characteristic curve (AUC) of 0.716 (95% confidence interval, 0.6914-0.7406), an accuracy rate of 0.6081, a sensitivity rate of 0.7113, and a specificity rate of 0.505. Importance analysis indicated that semen volume was the most vital variable in predicting IUI clinical pregnancy. CONCLUSIONS: The machine learning-based IUI clinical pregnancy prediction model showed a promising predictive efficacy that could provide a potent tool to guide selecting targeted infertile couples beneficial from IUI treatment, and also identify which parameters are most relevant in IUI clinical pregnancy.

Low Estradiol Level and Endometrial Thickness on the Day of Endometrial Transformation Influence Clinical Pregnancy After Intrauterine Insemination.

Background: The causes of pregnancy failure after intrauterine insemination (IUI) are controversial. The purpose of this study was to investigate the influencing factors on clinical pregnancy after IUI. Methods: This study retrospectively analyzed 1464 cycles of IUI performed at the Meizhou People's Hospital between March 2014 and June 2023. The χ2 test and logistic regression analysis was applied to assess the associations between the some factors (maternal age, paternal age, cycle type (natural cycle or ovulation induction cycle), hormone level on the day of endometrial transformation (estradiol (E2), luteinizing hormone (LH), and progesterone (P)), endometrial thickness on the day of endometrial transformation, and forward motile sperm concentration after treatment) and pregnancy failure. Results: Among the 1464 IUI cycles in this study, 268 cycles of assisted reproduction resulted in clinical pregnancy, with a clinical pregnancy rate of 18.3%. During the cycles with clinical pregnancy, there were 25 (12.9%) preterm births and 169 (87.1%) full-term births. The E2 level on the day of endometrial transformation in clinical pregnancy group was higher than that in the pregnancy failure group (658.79±656.02 vs 561.21±558.83 pg/mL)(P=0.025). The clinical pregnancy group had a higher percentage of endometrial thickness between 8 and 13mm on the day of endometrial transformation than the pregnancy failure group (83.2% vs 75.0%)(P=0.002). The results of regressions analysis showed that low E2 level on the day of endometrial transformation (<238.3 pg/mL vs ≥238.3 pg/mL: OR 1.493, 95% CI: 1.086-2.052, P=0.014), and endometrial thickness <8mm on the day of endometrial transformation (<8mm vs 8-13mm: OR 1.886, 95% CI: 1.284-2.771, P=0.001) may increase risk of pregnancy failure performed IUI. Conclusion: Low estradiol level, and endometrial thickness on the day of endometrial transformation may increase risk of pregnancy failure performed intrauterine insemination.

Moving toward Narrowing the United States Gap in Assisted Reproductive Technology (ART) Racial and Ethnic Disparities in the Next Decade.

The Disparities in Assisted Reproductive Technology (DART) hypothesis, initially described in 2013 and further modified in 2022, is a conceptual framework to examine the scope and depth of underlying contributing factors to the differences in access and treatment outcomes for racial and ethnic minorities undergoing ART in the United States. In 2009, the World Health Organization defined infertility as a disease of the reproductive system, thus recognizing it as a medical problem warranting treatment. Now, infertility care is largely recognized as a human right. However, disparities in Reproductive Endocrinology and Infertility (REI) care in the US persist today. While several studies and review articles have suggested possible solutions to racial and ethnic disparities in access and outcomes in ART, few have accounted for and addressed the multiple complex factors contributing to these disparities on a systemic level. This review aims to acknowledge and address the myriad of contributing factors through the DART hypothesis which converge in racial/ethnic disparities in ART and considers possible solutions to effect large scale societal change by narrowing these gaps within the next decade.

Determinant Factors for Ongoing Pregnancy in Homologous Intrauterine Insemination Cycles - A Prospective Study.

BACKGROUND/AIM: Intrauterine insemination (IUI) is the most common assisted-reproduction treatment. However, it has lower success rate in comparison to other treatments. Therefore, determining factors that contribute to IUI success is of particular interest and this was the purpose of this prospective study. PATIENTS AND METHODS: In this study, only homologous inseminations with fresh semen samples were included. All women received mild ovarian stimulation with clomiphene citrate and gonadotropins. Before IUI, basic semen analysis, evaluation of DNA fragmentation index (DFI), as well as measurement of sperm redox potential, were performed on each semen sample. Semen was processed with density-gradient centrifugation and 500 µl of processed sperm was used for insemination. RESULTS: In 200 cycles, there were 36 pregnancies, six of them ectopic. Cycles with ongoing pregnancies were characterized by younger male and female age and higher number of follicles. Multivariate logistic regression analysis showed that only female age was significantly associated with ongoing pregnancy. DFI was positively correlated with male age and negatively correlated with sperm concentration and progressive motility. Semen redox potential showed a strong negative correlation with sperm concentration and positive correlation with DFI. CONCLUSION: Female age seems to be the most important determinant factor for the achievement of an ongoing pregnancy in homologous IUI cycles with fresh semen.

Rescue intrauterine insemination in women failing to retrieve oocytes at ovum pick-up: report of a case series.

PURPOSE: Failure to collect oocytes at the time of oocyte pick-up is an unfavorable outcome of in vitro fertilization (IVF) cycles. In these cases, prompt intrauterine insemination (IUI) could be an option (rescue IUI), but this possibility has been poorly studied. METHODS: Rescue IUI is routinely offered in our unit in women failing to retrieve oocytes, provided that they have at least one patent tube, normal male semen analysis, and the total number of developed follicles is ≤ 3. We therefore reviewed all oocyte retrievals performed from 2006 to 2022 in our unit to identify these cases. As a comparator, we referred to preplanned IUI performed during the same study period. The 95% confidence interval (95% CI) of proportions was calculated using a binomial distribution model. RESULTS: Rescue IUI was performed in 96 out of 3531 oocyte retrievals (2.7%; 95% CI 2.2-3.3%). Six live births were obtained, corresponding to 6.2% (95% CI 2.3-13.1). All pregnancies were singletons. CONCLUSIONS: Rescue IUI in women failing to retrieve oocytes is a possible option that may be considered in selected cases. The efficacy is low, but the procedure is simple, and without significant risks. Generalizability to a conventional IVF protocol setting is however limited.

The impact of estradiol supplementation on endometrial thickness and intrauterine insemination outcomes.

The impact of estrogen supplementation during the follicular/proliferative phase on the endometrial lining thickness (EMT) prior to intrauterine insemination (IUI) remains largely unstudied. Our study examined changes in EMT and rates of clinical pregnancy, miscarriage, and live birth for all patients who completed an IUI cycle at Stanford Fertility Center from 2017-2023 (n = 2281 cycles). Cycles with estradiol supplementation (n = 309) were compared to reference cycles without supplementation (n = 1972), with the reference cohort further categorized into cycles with a pre-ovulatory EMT of < 7 mm ("thin-lining", n = 536) and ≥ 7 mm ("normal-lining", n = 1436). The estradiol group had a statistically significant greater change in EMT from baseline to ovulation compared to the thin-lining reference groups (2.4 mm vs 1.9 mm, p < =0.0001). Similar rates of clinical pregnancy and live birth were observed. After adjusting for age, BMI, race/ethnicity, infertility diagnosis, and EMT at trigger, the estradiol cohort had a significantly increased odds of miscarriage versus the entire reference cohort (2.46, 95 % confidence interval [1.18, 5.14], p = 0.02). Thus, although estradiol supplementation had a statistically significant increase in EMT compared to IUI cycles with thin pre-ovulatory EMT (<7 mm), this change did not translate into improved IUI outcomes such as increased rates of clinical pregnancy and live birth or decreased rate of miscarriage. Our study suggests that supplemental estradiol does not appear to improve IUI outcomes.

Effects of male hepatitis B virus infection and serostatus on sperm quality, pregnancy outcomes, and neonatal outcomes following intrauterine insemination.

OBJECTIVE: To evaluate the impact of male hepatitis B virus (HBV) infection and serostatus on sperm quality, pregnancy outcomes, and neonatal outcomes following intrauterine insemination for infertility. DESIGN AND METHODS: We retrospectively analyzed data from 962 infertile couples undergoing intrauterine insemination treatment at a single center. The case group comprised 212 infertile couples with male HBV infection, and the control group comprised 750 noninfected infertile couples. The couples were further divided into subgroups according to their hepatitis B e antigen (HBeAg)/anti-HBe status: hepatitis B surface antigen (HBsAg)+HBeAg- (group A), HBsAg+HBeAg+ (group B), and HBsAg-HBeAg- (control group). The main outcome parameters, including the seminal parameters, clinical pregnancy rate, miscarriage rate, live birth rate, preterm delivery rate, multiple pregnancy rate, delivery type, birth weight, and sex ratio, were compared. RESULTS: A lower sperm acrosin activity, higher cesarean rate, and newborn sex ratio were observed in the HBV-infected group and group A in comparison with the control group (P < 0.05). However, the standard sperm parameters, clinical pregnancy rate, miscarriage rate, live birth rate, preterm delivery, and birth weight showed no statistically significant differences among the groups. CONCLUSION: Male HBV infection does not adversely impact standard sperm parameters or pregnancy outcomes but can influence sperm acrosin activity and some neonatal outcomes. Moreover, the effect may vary among different HBV serostatuses.

Cumulative live birth rates following intrauterine insemination using donor and husband sperm in different age groups: A cohort study of 10 415 insemination cycles.

OBJECTIVES: To assess the age-specific cumulative live birth rates (CLBRs) in intrauterine insemination (IUI) cycles using either donor or husband sperm, and to investigate the impact of sperm sources on IUI success among women within the same age group. METHODS: This retrospective cohort study comprised women who underwent IUI with donor sperm (IUI-D) or husband sperm (IUI-H) from 2017 to 2021. The women were stratified based on their age at the initiation of insemination into four categories: <35, 35-37, 38-39 and ≥40 years. RESULTS: A total of 5253 women undergoing 10 415 insemination cycles (3354 with IUI-D and 7061 with IUI-H) were included. The CLBRs decreased significantly with increasing maternal age within donor and husband insemination groups (P < 0.001). In the IUI-D group, the crude CLBRs were 61.50% in women aged <35, 48.91% in 35-37, 24.14% in 38-39 and 11.76% in the ≥40-year age category, respectively. The corresponding rates in the IUI-H group were 27.62%, 22.96%, 13.73% and 6.90%, respectively. Within the <35 and 35-37-year age categories, the CLBRs were significantly higher following IUI-D cycles compared to IUI-H cycles, with hazard ratios (HR) of 1.85 (1.68-2.04) and 1.69 (1.16-2.47), respectively. However, within the 38-39 and ≥40-year age categories, both IUI-D and IUI-H resulted in comparable low CLBRs, with HRs of 1.91 (0.77-4.76) and 1.80 (0.33-9.86), respectively. CONCLUSION: Advanced maternal age affects the whole process of fertility. Therefore, it could be reasonable to limit the number of IUI performed in women aged 40 years and older, even in couple using donor sperm for reproduction.

The impact of thyroid autoimmunity on pregnancy outcomes in women with unexplained infertility undergoing intrauterine insemination: a retrospective single-center cohort study and meta-analysis.

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.

Effect of follicle size on pregnancy outcomes in patients undergoing first letrozole-intrauterine insemination.

BACKGROUND: Letrozole has been proven to be an effective method for inducing ovulation. However, little attention has been paid to whether the lead follicle size will affect the success rate of intrauterine insemination (IUI) with ovulation induction with alone letrozole. Therefore, we hope to investigate the effect of dominant follicle size on pregnancy outcomes on human chorionic gonadotropin (hCG) day of the first letrozole-IUI. METHODS: A retrospective cohort study design was employed. We included patients with anovulation or unexplained infertility undergoing first IUI treatment with letrozole for ovarian stimulation. According to the dominant follicle size measured on the day of hCG trigger, patients were divided into six groups (≤ 18 mm, 18.1-19.0 mm, 19.1-20.0 mm, 20.1-21.0 mm, 21.1-22.0 mm, > 22 mm). Logistic models were used for estimating the odds ratios (ORs) with their 95% confidence interval (CIs) for achieving a clinical pregnancy or a live birth. A restricted cubic spline was drawn to explore the nonlinear relationship between follicle size and IUI outcomes. RESULTS: A total of 763 patients underwent first letrozole-IUI cycles in our study. Fisher exact test showed significant differences among the six follicle-size groups in the rates of pregnancy, clinical pregnancy and live birth (P < 0.05 in each group). After adjusting the potential confounding factors, compared with the follicles ≤ 18 mm in diameter group, 19.1-20.0 mm, 20.1-21.0 mm groups were 2.3 or 2.56 times more likely to get live birth [adjusted OR = 2.34, 95%CI (1.25-4.39); adjusted OR = 2.56, 95% CI (1.30-5.06)]. A restricted cubic spline showed an inverted U-shaped relationship between the size of dominant follicles and pregnancy rate, clinical pregnancy rate, and live birth rate, and the optimal follicle size range on the day of hCG trigger was 19.1-21.0 mm. When the E2 level on the day of hCG trigger was low than 200 pg/mL, the clinical pregnancy rates of 19.1-20.0 mm, 20.1-21.0 mm groups were still the highest. CONCLUSIONS: The optimal dominant follicle size was between 19.1 and 21.0 mm in hCG-triggered letrozole-IUI cycles. Either too large or too small follicles may lead to a decrease in pregnancy rate. Using follicle size as a predicator of pregnancy outcomes is more meaningful when estrogen on the day of hCG trigger is less than 200 pg/ml.

Comparison of two cancellation strategies to lower the risk of multiple pregnancies in gonadotropin stimulated intrauterine insemination cycles.

OBJECTIVE: To compare two cancellation policies in controlled ovarian stimulation-intrauterine insemination (COS-IUI) cycles to lower the risk of multiple pregnancies (MP). DESIGN: We performed a bicentric retrospective cohort study in two academic medical centers: Angers (group A) and Besançon (group B) University Hospitals. We included 7056 COS-IUI cycles between 2011 and 2019. In group A, cancellation strategy was based on an algorithm taking into account the woman's age, the serum estradiol level, and the number of follicles of 14 mm or greater on ovulation trigger day. In group B, cancellation strategy was case-by-case and physician-dependent, based on the woman's age, number of follicles of 15 mm or greater, and the previous number of failed COS-IUI cycles, without any predefined cut-off. Our main outcome measures were the MP rate (MPR) and the live-birth rate (LBR). RESULTS: We included 884 clinical pregnancies (790 singletons, 86 twins, and 8 triplets) obtained from 6582 COS-IUI cycles. MPR was significantly lower in group A compared with group B (8.1% vs 13.3%, P = 0.01), but LBR were comparable (10.8% vs 11.8%, P = 0.19). Multivariate logistic regression found the following to be risk factors for MP: the "cancellation strategy" effect (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.02-2.60) and the number of follicles of 14 mm or greater (aOR 1.39, 95% CI 1.16-1.66). Cycle cancellation rate for excessive response was significantly lower in group A compared with group B (1.3% vs 2.4%, P < 0.001). CONCLUSIONS: The use of an algorithm based on the woman's age, serum estradiol level and number of follicles of at least 14 mm on trigger day allows the MPR to be reduced without impacting the LBR.

Intrauterine insemination: prognostic factors.

OBJECTIVE: To evaluate the impact of possible maternal and paternal prognostic factors and ovarian stimulation protocols on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles. METHODS: Retrospective observational study of 341 IUI cycles performed from January 2016 to November 2020 at the Assisted Reproduction Service of the Clinics Hospital of the Ribeirão Preto Medical School, University of São Paulo. Clinical pregnancy and live birth rates and their potential prognostic factors were evaluated. Wilcoxon's non-parametric test was used to compare quantitative variables, and the chi-square test to compare qualitative variables, adopting a significance level of p<0.05. A logistic regression model was performed to verify which exploratory variables are predictive factors for pregnancy outcome. RESULTS: The ovulation induction protocol using gonadotropins plus letrozole (p=0.0097; OR 4.3286, CI 1.3040 - 14.3684) and post-capacitation progressive sperm ≥ 5million/mL (p=0.0253) showed a statistically significant correlation with the live birth rate. Female and male age, etiology of infertility, obesity, multifollicular growth, endometrial thickness ≥ 7 mm, and time between human chorionic gonadotropin administration and IUI performance were not associated with the primary outcomes. In the group of patients with ideal characteristics (women aged< 40 years, BMI < 30 kg/m2, antral follicle count ≥ 5, partner aged< 45 years, and post-capacitation semen with progressive spermatozoa ≥ 5 million/mL), the rate of clinical pregnancy was 14.8%, while that of live birth, 9.9%. CONCLUSIONS: In this study, the ovulation induction protocol with gonadotropins plus letrozole and post-capacitation progressive sperm ≥ 5 million/mL were the only variables that significantly correlated with intrauterine insemination success.

[Pregnancy after intrauterine insemination following hysterosalpingo-foam-sonography or hysterosalpingography]. / Grossesse par insémination intra-utérine après hystérosalpingo-foam-sonographie ou hystérosalpingographie.

OBJECTIVE: To compare clinical pregnancy rates following intrauterine insemination performed after hysterosalpingography (HSG) or hysterosalpingo-foam-sonography (HyFoSy). MATERIAL AND METHODS: This is a retrospective study including 242 intrauterine insemination (IUI) performed between 2015 and 2020 at the fertility center of the Reunion Island. Among these inseminations, 121 with previous HSG and 121 with previous HyFoSy were matched. The main outcome of interest was clinical pregnancy rate. Secondary outcomes were birth rate and time to pregnancy after tubal patency test. RESULTS: The pregnancy rate after insemination was 9.9% for the HSG group and 11.6% for the HyFoSy group, with no statistically significant difference between the groups (P=0.66). The live birth rate was similar in the two groups (7.4% for HSG and 10.7% for HyFoSy; P=0.37). Over half (57.1%) of the pregnancies occurred within 6 months after HyFoSy, whereas only 8.3% after HSG. CONCLUSION: IUI results are not influenced by HyFoSy compared to HSG with regard to the pregnancy rates. Use of HyFoSy in infertility assessment allows global evaluation and more rapid adapted management. This approach could optimize management of patients undergoing IUI.