Predictive factors for intrauterine insemination outcomes: a review

Le M.T., Nguyen T.A., Nguyen H.T., Nguyen T.T., Nguyen V.T., Le D.D., Nguyen V.Q., Cao N.T.

This study aimed to investigate the association between sperm quality assessed by routine semen analysis and sperm DNA integrity assay.In our cross-sectional study, a total of 318 men from the infertile couples were enrolled from December 2017 to March 2019 at the Hue Center for Reproductive Endocrinology and Infertility, Vietnam. General characteristics and semen parameters were detected. The sperm DNA fragmentation index (DFI) was estimated by the sperm chromatin dispersion (SCD) assay. A threshold of DFI 30% was applied to classify normal (DFI < 30%) or abnormal (DFI ≥ 30%) groups. The correlations between DFI and semen parameters were analyzed by Spearman's rank correlation coefficient.In the correlation analysis, DFI was significantly correlated with abnormal head and progressive motility, with a positive correlation with abnormal head (ρ = .202, P = .0003) and a weak negative correlation with progressive motility (ρ = -.168, P = .0027), respectively. In the bivariate analysis, DFI was associated with male age, smoking, and alcohol consumption with P < .05.The sperm DFI was not strongly correlated with conventional semen parameters. Therefore, a sperm DNA fragmentation assay should be performed as an additional step in the investigation of male fertility.

Gubert P.G., Pudwell J., Van Vugt D., Reid R.L., Velez M.P.

To determine whether age modifies the effect of the number of motile spermatozoa inseminated (NMSI) as a predictor of success in Intrauterine Insemination (IUI). This retrospective cohort study included all patients who underwent IUI at an academic infertility center between October 2004 and June 2018. The primary outcome was clinical pregnancy (CP; a gestational sac and fetal heartbeat on ultrasound). Results were analyzed by patient factors including age, NMSI, duration of infertility, and cause of infertility, along with treatment factors such as number of follicles and ovulation induction protocol. Factors associated with the odds of achieving a clinical pregnancy were analyzed using binary logistic generalized estimating equations to control for clustering effects by couple. Female age was categorized as <35 years vs. ≥35 years. Seven hundred thirty-seven couples that underwent 2062 IUI cycles for heterogeneous indications were included. The overall CP rate was 15.1% per cycle, and the cumulative CP rate per couple was 35.9%. For females < 35 years, the odds of CP per cycle were reduced for NMSI categories (× 106) of < 5.0 vs. ≥10.0 (OR = 0.49; 95% CI 0.29–0.83); the odds of CP per cycle did not differ for NMSI 5.0–9.9 vs. ≥10.0 (OR = 0.66; 0.37–1.18). For those ≥35 years, no difference was seen in the odds of CP per cycle for NMSI categories < 5.0 vs. ≥10.0 (OR = 1.55; 95% CI 0.72–3.31) or 5.0–9.9 vs. ≥10.0 (OR = 1.04; 95% CI 0.48–2.27). These results suggest that the NMSI can be used as a predictor of success in IUI in couples with women who are < 35 years of age; these patients should be counselled about their lower pregnancy rates when the NMSI is < 5.0 × 106. In patients ≥35 years, the NMSI does not appear to be a useful predictor of success. Further studies with larger sample size should be conducted.

Yang H., Li G., Jin H., Guo Y., Sun Y.

The sperm DNA fragmentation index (DFI) is widely regarded as a key measure for assessing male fertility, but the predictive value of the DFI for outcomes of assisted reproductive technology (ART) remains under debate. In this study, we used a large sample to analyze the effect of sperm DFI on pregnancy outcomes following ART and its relationship with oocyte fertilization and embryo development in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). We also explore the value of sperm DNA fragmentation (SDF) and its associated factors in assessing male fertility.The relationship between the DFI measured with the sperm chromatin structure assay (SCSA) and pregnancy outcomes following ART were retrospectively analyzed in 2,622 ART treatment cycles, of which 1,185 were intrauterine insemination (IUI) cycles, 1,221 were IVF cycles and 216 were ICSI cycles. Rates of pregnancy, early abortion, oocyte fertilization and good quality embryos from IVF and ICSI cycles were compared between the groups of low DFI (DFI ≤15%), medium DFI (15%< DFI

Mankus E.B., Holden A.E., Seeker P.M., Kampschmidt J.C., McLaughlin J.E., Schenken R.S., Knudtson J.F.

Objective To determine whether there is a relationship between prewash total motile count and live births in couples undergoing IUI. Design Retrospective review in a single academic center. Setting Not applicable. Patient(s) Couples with infertility undergoing ovulation induction with IUI between 2010 and 2014. Intervention(s) Not applicable. Main Outcome Measure(s) Live births. Result(s) Our cohort included 310 women who underwent 655 IUI cycles with a cumulative live birth rate (LBR) per couple of 20% and an LBR per cycle of 10%. A analysis yielded no correlation between prewash total motile count (TMC) and live births. No live births occurred with TMC 37 years (90% sensitivity, 70% specificity). The LBR per couple was decreased to 7% in women >37 years compared with 25% in women Conclusion(s) Prewash TMC is a poor predictor of live birth. There were no live births with prewash TMC 37 years with IUI was significantly lower than women

Cohlen B., Bijkerk A., Van der Poel S., Ombelet W.

IUI with or without ovarian stimulation (OS) has become a first-line treatment option for many infertile couples, worldwide. The appropriate treatment modality for couples and their clinical management through IUI or IUI/OS cycles must consider maternal and perinatal outcomes, most notably the clinical complication of higher-order multiple pregnancies associated with IUI-OS. With a current global emphasis to continue to decrease maternal and perinatal mortality and morbidity, the World Health Organization (WHO) had established a multi-year project to review the evidence for the establishment of normative guidance for the implementation of IUI as a treatment to address fertility problems, and to consider its cost-effectiveness for lower resource settings.The objective of this review is to provide a review of the evidence of 13 prioritized questions that cover IUI with and without OS. We provide summary recommendations for the development of global, evidence-based guidelines based upon methodology established by the WHO.We performed a comprehensive search using question-specific relevant search terms in May 2015. For each PICO (Population, Intervention, Comparison and Outcomes) drafted by WHO, specific search terms were used to find the available evidence in MEDLINE (1950 to May 2015) and The Cochrane Library (until May 2015). After presentation to an expert panel, a further hand search of references in relevant reviews was performed up to January 2017. Articles that were found to be relevant were read and analysed by two investigators and critically appraised using the Cochrane Collaboration's tool for assessing risk of bias, and AMSTAR in case of systematic reviews. The quality of the evidence was assessed using the GRADE system. An independent expert review process of our analysis was conducted in November 2016.This review provides an assessment and synthesis of the evidence that covers 13 clinical questions including the indications for the use of IUI versus expectant management, the sperm parameters required, the best and optimal method of timing and number of inseminations per cycle, prevention strategies to decrease multiple gestational pregnancies, and the cost-effectiveness of IUI versus IVF. We provide an evidence-based formulation of 20 recommendations, as well as two best practice points that address the integration of methods for the prevention of infection in the IUI laboratory. The quality of the evidence ranges from very low to high, with evidence that may be decades old but of high quality, however, we further discuss where critical research gaps in the evidence remain.This review presents an evidence synthesis assessment and includes recommendations that will assist health care providers worldwide with their decision-making when considering IUI treatments, with or without OS, for their patients presenting with fertility problems.

Craig L.B., Weedin E.A., Walker W.D., Janitz A.E., Hansen K.R., Peck J.D.

No research exists on American Indian pregnancy rates following infertility treatment. Most racial/ethnic fertility research has focused on pregnancy following in vitro fertilization, with only rare studies looking at intrauterine insemination (IUI). The objective of our study was to compare fecundability following IUI by race/ethnicity, with a special focus on American Indians. This was a retrospective analysis of subjects undergoing IUI July 2007–May 2012 at a university-based infertility clinic. The primary outcome was positive pregnancy test, with a secondary outcome of ongoing pregnancy/delivery (OP/D). We calculated risk ratios (RR) and 95% confidence intervals (CI) using cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient. A total of 663 females (median age 32) undergoing 2007 IUI cycles were included in the analysis. Pregnancy rates overall were 15% per IUI cycle. OP/D rates overall were 10% per IUI cycle. The American Indian patients had significantly lower pregnancy (RR 0.34, 95% CI 0.16–0.72) and OP/D rates (RR 0.33, 95% CI 0.12–0.87) compared to non-Hispanic whites when patient and cycle characteristics were controlled. Pregnancy and OP/D rates for blacks, Asians, and Hispanics did not differ from those of non-Hispanic whites. Our finding of lower IUI treatment success among American Indian patients is novel, as no published studies of assisted reproductive technology or other fertility treatments have examined this subgroup separately. Further investigation of patient and clinical factors that may mediate racial/ethnic disparities in fertility treatment outcomes is warranted.

van Rijswijk J., Caanen M.R., Mijatovic V., Vergouw C.G., van de Ven P.M., Lambalk C.B., Schats R.

Does 15 min of immobilization after IUI improve pregnancy rates?Immobilization for 15 min after IUI does not improve pregnancy rates.Prior RCTs report a beneficial effect of supine immobilization for 15 min following IUI compared to immediate mobilization, however, these studies can be criticized. Given the importance for the logistics in daily practice and the lack of biological plausibility we planned a replication study prior to potential implementation of this procedure.A single centre RCT, based in an academic setting in the Netherlands, was performed. Participants were randomly assigned for 15 min of supine immobilization following IUI for a maximum of six cycles compared to the standard procedure of immediate mobilization following IUI. Participants and caregivers were not blinded to group assignment. An independent researcher used computer-generated tables to allocate treatments. Stratification occurred to the indication of IUI (unexplained or mild male subfertility). Revelation of allocation took place just before the insemination by the caregiver. The primary outcome was ongoing pregnancy rate per couple.A total of 498 couples diagnosed with unexplained or mild male subfertility and an indication for treatment with IUI were approached and randomized in the study, of which 244 participants were assigned to 15 min of supine immobilization and 254 participants to immediate mobilization.Participant characteristics were comparable between the groups, and 236 participants were analysed in the immobilization group, versus 245 in the mobilization group. The ongoing pregnancy rate per couple was not found to be superior in the immobilization group (one-sided P-value = 0.97) with 76/236 ongoing pregnancies (32.2%) being accomplished in the immobilization and 98/245 ongoing pregnancies (40.0%) in the immediate mobilization group (relative risk 0.81; 95% CI [0.63, 1.02], risk difference: -7.8%, 95% CI [-16.4%, 0.8%]). No difference was found in miscarriage rate, multiple gestation rate, live birth rate and time to pregnancy between the groups.Owing to discontinuation of the planned treatment not all participants reached six IUI cycles or an ongoing pregnancy. However, this is as expected in IUI treatment and mirrors clinical practice. These participants were equally distributed across the two groups. Women with tubal pathology and endocrine disorders were excluded for this trial, and this might narrow generalizability.This study shows no positive effect of 15 min of immobilization following IUI on pregnancy rates. Based on available evidence today, including our study, a possible beneficial effect of supine immobilization after IUI is at least doubtful and straightforward implementation does not seem to be justified.No funding was received. All authors have nothing to disclose.Dutch Trial Register NTR 2418.20 July 2010.11 August 2010.

El Hachem H., Antaki R., Sylvestre C., Lapensée L., Legendre G., Bouet P.E.

This cohort study assessed whether timing therapeutic donor sperm inseminations (TDI) in natural cycles (NC) using ultrasound monitoring and ovulation trigger with human chorionic gonadotrophin (US/HCG) improves cumulative live birth rates (LBR) compared with detection of LH surge with urinary kits (u-LH). It included 232 normo-ovulatory women aged ≤40 years, undergoing 538 TDI in NC between 2011 and 2014. In the u-LH group (113 women, 267 cycles), TDI was performed the day following a positive test. In the US/HCG group (119 women, 271 cycles), ovulation was triggered with HCG when a follicle ≥17 mm was noted, and TDI performed 36 h later. The first three cycles were analysed per patient. Groups were comparable for baseline characteristics. Cumulative LBR were comparable between u-LH and US/HCG groups (31.47% versus 23.11%, respectively) (log-rank test). A generalized estimating equation analysis was performed to compare outcomes per cycle. The LBR per started cycle was comparable between the u-LH and US/HCG groups (12.4% versus 9.2%, respectively). Cancellation rate was significantly higher with u-LH (19.1% versus 11.4%, P = 0.011), but did not impact overall outcomes. In conclusion, urinary LH monitoring is as effective as ultrasound monitoring and ovulation trigger with HCG in TDI performed in NC.

Barratt C.L., Björndahl L., De Jonge C.J., Lamb D.J., Osorio Martini F., McLachlan R., Oates R.D., van der Poel S., St John B., Sigman M., Sokol R., Tournaye H.

Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility.

El Hachem H., Antaki R., Sylvestre C., Kadoch I., Lapensée L., Bouet P.E.

<b><i>Aim:</i></b> To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. <b><i>Methods:</i></b> Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). <b><i>Results:</i></b> Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. <b><i>Conclusion:</i></b> In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates.

Hansen K.R., He A.L., Styer A.K., Wild R.A., Butts S., Engmann L., Diamond M.P., Legro R.S., Coutifaris C., Alvero R., Robinson R.D., Casson P., Christman G.M., Huang H., Santoro N., et. al.

To identify baseline characteristics of couples that are likely to predict conception, clinical pregnancy, and live birth after up to four cycles of ovarian stimulation with IUI in couples with unexplained infertility.Secondary analyses of data from a prospective, randomized, multicenter clinical trial investigating pregnancy, live birth, and multiple pregnancy rates after ovarian stimulation-IUI with clomiphene citrate, letrozole, or gonadotropins.Outpatient clinical units.Nine-hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial.As part of the clinical trial, treatment was randomized equally to one of three arms and continued for up to four cycles or until pregnancy was achieved.Conception, clinical pregnancy, and live-birth rates.In a multivariable logistic regression analysis, after adjustment for other covariates, age, waist circumference, income level, duration of infertility, and a history of prior pregnancy loss were significantly associated with at least one pregnancy outcome. Other baseline demographic and lifestyle characteristics including smoking, alcohol use, and serum levels of antimüllerian hormone were not significantly associated with pregnancy outcomes.While age and duration of infertility were significant predictors of all pregnancy outcomes, many other baseline characteristics were not. The identification of level of income as a significant predictor of outcomes independent of race and education may reflect differences in the underlying etiologies of unexplained infertility or could reveal disparities in access to fertility and/or obstetrical care.NCT01044862.

Dimitriadis I., Batsis M., Petrozza J.C., Souter I.

Studies suggest that race may affect access to fertility treatments and their outcomes. We examined whether race affects the following: duration of infertility prior to seeking evaluation, diagnosis, treatment cycle characteristics, and outcomes. Design: Retrospective cohort. Settings: Academic fertility center. Patients: 4537 intrauterine insemination ± ovulation induction (IUI ± OI) cycles/1495 patients. Interventions: IUI following: (i) OI with either clomiphene citrate or gonadotropins and (ii) ultrasound-monitored natural cycles. Outcome measures: Duration of infertility prior to seeking treatment, SART diagnosis, treatment cycle characteristics and outcomes (spontaneous abortion (SABR), clinical (CPR) and multiple pregnancy rates (MPR)). Asians and Hispanics compared to Caucasians waited significantly longer prior to seeking fertility evaluation (p < 0.01). The mean age of patients seeking infertility evaluation did not differ between groups nor did the type of treatment initially chosen by the patients. Idiopathic infertility was more common among Caucasians (p < 0.05, compared to all others) while PCOS and tubal factor infertility were more frequent among Hispanics (p < 0.05, compared to Caucasian, Asian, and mixed ancestry women) and decreased ovarian reserve was more common among African-Americans (p < 0.01, compared to Caucasians, Asians, and Hispanics). Gonadotropin cycle characteristics including dosing and duration of treatment, follicular recruitment, peak estradiol levels, and endometrial lining thickness differed between certain groups. However, no difference was found in CPR, MPR, and SABR between groups. Race affects timely access to infertility care, diagnosis, and treatment cycle characteristics but not outcomes. Considering the nation’s growing multiracial population, understanding the effect of race on fertility care becomes increasingly important.

Diamond M.P., Legro R.S., Coutifaris C., Alvero R., Robinson R.D., Casson P., Christman G.M., Ager J., Huang H., Hansen K.R., Baker V., Usadi R., Seungdamrong A., Bates G.W., Rosen R.M., et. al.

The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates.We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies.After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P

Crawford N.M., Steiner A.Z.

Oocyte number and quality decrease with advancing age. Thus, fecundity decreases as age increases, with a more rapid decline after the mid-30s. Patients more than 35 years old should receive prompt evaluation for causes of infertility after no more than 6 months of attempted conception. Patients with abnormal tests of ovarian reserve have a poorer prognosis and may need more expedited and aggressive treatment. Although oocyte donation is the best method to overcome age-related infertility, other treatment options may help women proceed quicker toward pregnancy. Patients at an advanced age should be counseled and evaluated before undergoing infertility treatments.

Abualiat Z., Alanazi D., Alanazi M., Alwan M., Yaqoub R., Alhomrani A., Alsomali N.

Trabaud V., Miquel L., Faust C., Berbis J., Paulmyer-Lacroix O., Courbiere B.

Chronopoulou E., Gaetano‐Gil A., Shaikh S., Raperport C., Al Wattar B.H., Ruiz‐Calvo G., Zamora J., Bhide P.

AbstractIntroductionIntrauterine insemination (IUI) is one of the most widespread fertility treatments. However, IUI protocols vary significantly amongst fertility clinics. Various add‐on interventions have been proposed to boost success rates. These are mostly chosen arbitrarily or empirically. The aim of this systematic review and meta‐analysis is to assess the effectiveness and safety of add‐on interventions to the standard IUI protocol and to provide evidence‐based recommendations on techniques used to optimize the clinical outcomes of IUI treatment.Material and MethodsSystematic review and meta‐analyses were performed in accordance with PRISMA guidelines. A computerized literature search was performed from database inception to May 2023. Randomized controlled trials (RCTs) were included reporting on couples/single women undergoing IUI with any protocol for any indication using partner's or donor sperm. A meta‐analysis based on random effects was performed for each outcome and add‐on. Three authors independently assessed the trials for quality and risk of bias and overall certainty of evidence. Uncertainties were resolved through consensus. Primary outcomes were ongoing pregnancy rate (OPR) or live birth rate (LBR) per cycle/per woman randomized. Registration number PROSPERO: CRD42022300857.ResultsSixty‐six RCTs were included in the analysis (16 305 participants across 20 countries). Vaginal progesterone as luteal phase support in stimulated cycles was found to significantly increase LBR/OPR (RR 1.37, 95% CI 1.09–1.72, I2 = 4.9%) (moderate/low certainty of the evidence). Endometrial scratch prior/during stimulated IUI cycles may increase LBR/OPR (RR 1.44, 95% CI 1.03–2.01, I2 = 1.8%), but evidence is very uncertain. Results from two studies suggest that follicular phase ovarian stimulation increases LBR/OPR (RR 1.39, 95% CI 1.00–1.94, I2 = 0%) (low certainty of evidence). No significant difference was seen for the primary outcome for the other studied interventions.ConclusionsThe findings of this systematic review and meta‐analysis suggest that vaginal luteal phase progesterone support probably improves LBR/OPR in stimulated IUI treatments. In view of moderate/low certainty of the evidence more research is needed for solid conclusions. Further research is also recommended for the use of endometrial scratch and ovarian stimulation. Future studies should report on results according to subfertility background as it is possible that different add‐ons could benefit specific patient groups.

Evans M.B., Hosseinzadeh P., Flannagan K., Jahandideh S., Burruss E., Peck J.D., Hansen K.R., Hill M., Devine K.

OBJECTIVE To study the primary objective of clinical pregnancy rate per ovarian stimulation intrauterine insemination cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN Retrospective cohort. SETTING Large fertility clinic. PATIENTS A total of 37,565 consecutive ovarian stimulation intrauterine insemination cycles from 18,509 patients were included in this study. INTERVENTIONS Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. Clinical pregnancy rate was analyzed by generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURE(S) Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS A total of 37,565 consecutive ovarian stimulation intrauterine insemination cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients < 35 years old comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of clinical pregnancy for cycles 1-8 was 15.7% per cycle. The mean predicted probability of clinical pregnancy in aggregated data from cycles 2-4 was only 1.7% lower compared to cycle 1 as the referent (16.7% vs. 15.0%, 95% CI 2nd: 0.88 (0.82, 0.95), 3rd: 0.86 (0.79, 0.93), 4th: 0.88 (0.79, 0.98)). However, the 15.0% mean predicted probability of clinical pregnancy for the 2nd through 4th cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of clinical pregnancy of cycles 5-8 was not significantly different when compared to the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 (0.85, 1.11), 6th: 0.93 (0.79, 1.10), 7th: 1.01 (0.81, 1.26), 8th: 1.01 (0.76, 1.34)). Modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of clinical pregnancy from OS-IUI continues to increase with each of the eight successive cycles. CONCLUSION Clinical pregnancy rates are satisfactory in up to 8 consecutive ovarian stimulation intrauterine insemination cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Lu Y., Cherouveim P., Jiang V., Dimitriadis I., James K.E., Bormann C., Souter I.

ObjectiveTo 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.MethodsRetrospective 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.ResultsIn 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&lt;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&lt;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&lt;0.001, p&lt;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.ConclusionsWithin-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.

Patil R., Jadhao R., Anjankar N., More A., Gajabe G., Shrivastava J.

ABSTRACT A couple visited the IVF clinic to seek treatment for primary infertility. A 45-year-old quadragenarian female and her 49-year-old male partner were recommended infertility treatment after 2 years of unsuccessful attempts to conceive. The woman had a recent history of dengue and chickenpox. The male partner was advised to do a semen analysis. The report showed asthenoteratozoospermia and the semen sample viscous. On the other hand, the female was diagnosed with hypothyroidism. The male patient was given a 3-month medication treatment that included probiotic supplements and cranberry juice to treat bacterial infections and urinary tract infections. The male partner also advised medication, and regular semen analysis was performed after every 3 months. The treatment plan included intrauterine insemination (IUI), which increased the possibility of pregnancy. Fourteen days following the IUI and pregnancy test, the outcomes were positive. The case illustrates the difficulties in treating primary infertility by combining reproductive procedures, medication, and lifestyle modifications. Regularly monitoring semen quality and hormonal levels is crucial in assessing treatment success. The positive outcome of IUI suggests the effectiveness of the fertility treatment plan.

Tang Q., Yi H., Chen S., Zheng Y., Wen Y., Yang M.

Huang C., Shi Q., Xing J., Yan Y., Shen X., Shan H., Sun H., Mei J.

Abstract Background The objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus. Methods A retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation. Results When the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817–0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643–0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800–0.998, p = 0.043). Conclusions The clinical pregnancy rate and live birth rate of IUI in young women (< 35 years old) who have been infertile for more than 5 years significantly decrease with the prolongation of infertility time. Therefore, for young women who have been infertile for more than 5 years, IUI may not be the best choice.

Yu C., Bai L., mei-Zhou J., yu-Wang X., Chen L., Zhang J.

Abstract Objective The objective of this study was to investigate the correlation between various factors and the clinical outcomes of Intrauterine Insemination (IUI) in both young and aged patients, aiming to provide a theoretical basis for clinical consultations. Methods This retrospective analysis examined a total of 4,221 IUI cycles conducted at the Reproductive Center of Changzhou Maternal and Child Health Hospital between January 2016 and December 2020. The patients were categorized into two groups based on age: the elder group (≥ 35 years) and the young group (< 35 years). Results The findings of this study revealed a significant association between woman’s age and BMI with pregnancy outcomes (0.93, 95% CI: 0.89–0.97) (1.04, 95% CI: 1.01–1.06). Moreover, in young women, both age and Body Mass Index (BMI)were found to be related to pregnancy outcomes (0.97, 95% CI: 0.89–0.97) (1.08, 95% CI: 1.01–1.06). Additionally, BMI and the number of cycles in aged IUI patients were found to be associated with pregnancy outcomes. The pregnancy rate in the second cycle was approximately 1.9 times higher than that in the first cycle (1.9, 95% CI: 0.97–3.77), and in the third cycle, it was approximately 3 times higher than that in the first cycle (3.04, 95% CI: 1.43–6.42). Conclusions In conclusion, there is an association between woman’s age and BMI and the clinical outcomes of IUI. However, the number of cycles did not affect the pregnancy outcomes in young women. Conversely, in elder women, the number of cycles was found to be related to the IUI pregnancy outcomes, with significantly higher pregnancy rates observed in the second and third cycles compared to the first cycle.

Yavuzcan A., Yurtçu E., Keyif B., Osmanlıoğlu Ş.

(1) Background: We aimed to investigate the effect of change in pre-wash and post-wash semen parameters on intrauterine insemination (IUI) success in a homogenous study group. (2) Methods: IUI cycles conducted at an infertility clinic were included in this study. Patient records were examined retrospectively. Δ sperm count (per mL) was calculated as [pre-wash sperm count (per mL)–post-wash sperm count (per mL)]. Δ Total progressive motile sperm count (TPMSC) was also calculated as (post-wash TPMSC-pre-wash TPMSC). (3) Results: No statistically significant difference was detected in terms of Δ sperm count (p = 0.38), and Δ TPMSC (p = 0.76) regarding the clinical pregnancy rate (CPR). There was no statistically significant difference between CPR (+) and CPR (−) groups in terms of post-wash sperm count, TPMSC, TPMSC ≥ 10 × 10⁶, TPMSC ≥ 5 × 10⁶ (p = 0.65, p = 0.79, p = 0.49, p = 0.49, respectively). The live birth rate (LBR) showed no statistically significant differences except for a pre-wash TPMSC ≥ 10 × 10⁶ (p = 0.02). Through the performed ROC analysis, no statistically significant cutoff value could be set for the pre-wash TPMSC. (4) Conclusions: There is only a pre-wash TPMSC ≥ 10 × 10⁶ that showed a significant role in the success of IUI, even when considering all other pre-wash and post-wash semen parameters. Δ sperm count and Δ are not useful markers for IUI success.

Kim H., Subramanian V., Baird F., Beebeejaun Y., Sarris I., Kamath M.S., Sunkara S.K.

Rachmawati A., Krisnadi S.R., Santoso S.A., Nugrahani A.D.

Abstract Objective There was also a lack of data regarding the effect of follicle size, endometrial thickness, and ovarian stimulation as predictors of intrauterine insemination (IUI) success rate in Indonesia, especially in the Aster Clinic and Bandung Fertility Centre. This study was performed to explore the relationship between follicle size, endometrial thickness, and types of ovarian stimulation (Clomiphene citrate/CC vs Letrozole) with biochemical pregnancy rate in women undergone IUI. We performed a case–control study in 122 women aged 20–40 years with unexplained infertility who had completed the IUI program for a maximum of three cycles. Data were extracted from medical records. Independent T-test and multivariate analyses were used to analyse the difference between variables using IBM SPSS 24.0. P-value < 0.05 was considered statistically significant. Result Follicle sizes of 18–22 mm in both Clomiphene citrate (CC) and Letrozole groups were shown to increase biochemical pregnancy rate (P = 0.001). There is no relationship between endometrial thickness and pregnancy rate. Biochemical pregnancy rate in women using Letrozole was 1.513 times higher than women using CC. The follicle size of 18–22 mm and using Letrozole rather than CC as ovarian stimulators are predictive factors associated with a higher pregnancy rate in women undergone IUI.

Sun Y.

To carry out an in-depth analysis of the scientific research on infertility, we performed the first bibliometric analysis focusing on studies involving global literature on infertility during the period 2013–2022. Analysis of 33239 articles in the field of infertility showed a significant increasing trend in the number of publications over the period 2013–2022, with authors mainly from the USA and China. Shanghai Jiao Tong University published the most articles. This study is the first to analyze the global field of infertility (2013–2022) from multiple indicators by bibliometrics, thus providing new insights into the research hotspots and development trends in the field of infertility.

Vagios S., Velmahos C.S., Cherouveim P., Dimitriadis I., Bormann C.L.

To assess the impact of 2 different sperm preparation methods, density gradient centrifugation and simple wash, on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles with and without ovulation induction.Retrospective single-center cohort study.Academic fertility center.In total, 1,503 women of all diagnoses sought IUI with fresh-ejaculated sperm.Cycles were divided into 2 groups on the basis of sperm preparation technique: density gradient centrifugation (n = 1,687, unexposed group) and simple wash (n = 1,691, exposed group).Primary outcome measures consisted of clinical pregnancy and live birth rates. Furthermore, adjusted odds ratios and 95% confidence intervals for each outcome were calculated and compared between the 2 sperm preparation groups.Odds ratios did not differ between density gradient centrifugation and simple wash groups for clinical pregnancy and live birth (1.10 [0.67-1.83] and 1.08 [0.85-1.37], respectively). Additionally, when cycles were stratified using ovulation induction rather than adjusted for, no differences in clinical pregnancy and live birth odds were noted between sperm preparation groups (gonadotropins: 0.93 [0.49-1.77] and 1.03 [0.75-1.41]; oral agents: 1.78 [0.68-4.61] and 1.05 [0.72-1.53]; unassisted: 0.08 [0.001-6.84] and 2.52 [0.63-10.00], respectively). Furthermore, no difference was seen in clinical pregnancy or live birth when cycles were stratified using sperm score or when the analysis was limited to first cycles only.Overall, no difference was noted in clinical pregnancy or live birth rates between patients who received simple wash vs. density gradient-prepared sperm, suggesting similar clinical efficacy between the 2 techniques for IUI. Because the simple wash technique is more time-efficient and cost-effective compared with the density gradient, adoption of this technique could lead to comparable clinical pregnancy and live birth rates for IUI cycles, although optimizing teamwork flow and coordination of care.

Cherouveim P., Vagios S., Hammer K., Fitz V., Jiang V.S., Dimitriadis I., Sacha C.R., James K.E., Bormann C.L., Souter I.

IntroductionFrozen sperm utilization might negatively impact cycle outcomes in animals, implicating cryopreservation-induced sperm damage. However, in vitro fertilization and intrauterine insemination (IUI) in human studies are inconclusive.MethodsThis study is a retrospective review of 5,335 IUI [± ovarian stimulation (OS)] cycles from a large academic fertility center. Cycles were stratified based on the utilization of frozen (FROZEN, n = 1,871) instead of fresh ejaculated sperm (FRESH, n = 3,464). Main outcomes included human chorionic gonadotropin (HCG) positivity, clinical pregnancy (CP), and spontaneous abortion (SAB) rates. Secondary outcome was live birth (LB) rate. Odds ratios (OR) for all outcomes were calculated utilizing logistic regression and adjusted (adjOR) for maternal age, day-3 FSH, and OS regimen. Stratified analysis was performed based on OS subtype [gonadotropins; oral medications (OM): clomiphene citrate and letrozole; and unstimulated/natural]. Time to pregnancy and cumulative pregnancy rates were also calculated. Further subanalyses were performed limited to either the first cycle only or to the partner's sperm only, after excluding female factor infertility, and after stratification by female age (&lt;30, 30–35, and &gt;35 years old).ResultsOverall, HCG positivity and CP were lower in the FROZEN compared to the FRESH group (12.2% vs. 15.6%, p &lt; 0.001; 9.4% vs. 13.0%, p &lt; 0.001, respectively), which persisted only among OM cycles after stratification (9.9% vs. 14.2% HCG positivity, p = 0.030; 8.1% vs. 11.8% CP, p = 0.041). Among all cycles, adjOR (95% CI) for HCG positivity and CP were 0.75 (0.56–1.02) and 0.77 (0.57–1.03), respectively, ref: FRESH. In OM cycles, adjOR (95% CI) for HCG positivity [0.55 (0.30–0.99)] and CP [0.49 (0.25–0.95), ref.: FRESH] favored the FRESH group but showed no differences among gonadotropin and natural cycles. SAB odds did not differ between groups among OM and natural cycles but were lower in the FROZEN group among gonadotropin cycles [adjOR (95% CI): 0.13 (0.02–0.98), ref.: FRESH]. There were no differences in CP and SAB in the performed subanalyses (limited to first cycles or partner's sperm only, after excluding female factors, or after stratification according to female age). Nevertheless, time to conception was slightly longer in the FROZEN compared to the FRESH group (3.84 vs. 2.58 cycles, p &lt; 0.001). No significant differences were present in LB and cumulative pregnancy results, other than in the subgroup of natural cycles, where higher LB odds [adjOR (95% CI): 1.08 (1.05–1.12)] and higher cumulative pregnancy rate (34% vs. 15%, p = 0.002) were noted in the FROZEN compared to the FRESH group.ConclusionOverall, clinical outcomes did not differ significantly between frozen and fresh sperm IUI cycles, although specific subgroups might benefit from fresh sperm utilization.