Insemination Cycles Research Articles

Intrauterine instillation of autologous platelet-rich plasma in infertile females with thin endometrium undergoing intrauterine insemination: an open-label randomized controlled trial

Thin endometrium in infertile female patients has always been a clinical challenge for the treating reproductive physicians. This study aimed to evaluate the effect of intrauterine instillation of autologous platelet-rich plasma on endometrial thickness and vascularity in infertile female patients with thin endometrium undergoing ovarian stimulation with intrauterine insemination. This prospective randomized control study included 120 women undergoing ovarian stimulation with intrauterine insemination, aged between 21 and 37 years, with persistent thin endometrium (<7 mm) on ≥1 cycle in previous ovarian stimulation cycles, even after conventional treatment with estradiol valerate. The women were randomly assigned to study group A and control group B. Baseline endometrial thickness and endometrial vascularity were noted. Intrauterine instillation of autologous platelet-rich plasma was done on the day of trigger in group A, whereas estradiol valerate was given in group B. Another evaluation of endometrial parameters was done on the day of intrauterine insemination. The cycle was repeated for 3 cycles or until the pregnancy was achieved, whichever occurred earlier. Parameters were noted for both groups. Primary outcomes were the change in endometrial thickness and endometrial vascularity. Secondary outcomes were positive pregnancy rate and clinical pregnancy rate. In group A, mean pre-platelet-rich plasma endometrial thickness was 4.66±0.79 mm, which significantly increased to 7.47±0.85 mm after platelet-rich plasma instillation (P<.05) after 3 cycles. This increase was significantly greater than that observed in group B. There was significant increase in endometrial vascularity in group A compared with group B (P<.05). The positive pregnancy rate and clinical pregnancy rate in group A were 23.73% and 18.64%, respectively, and significantly higher than those in group B. Autologous platelet-rich plasma is a promising, easily procurable, and novel option for management of infertile females with thin endometrium not responding to conventional treatment. Using it in intrauterine insemination cycles can reduce costs and psychological burden of this subgroup of women by reducing the need for resorting to advanced options such as in vitro fertilization and surrogacy.

The impact of anti-Müllerian hormone on endometrial thickness in gonadotropin stimulation/intrauterine insemination cycles: is there an effect on pregnancy outcomes?

To study the association, if any, between anti-Müllerian hormone (AMH) and pre-ovulatory endometrial thickness (ET) in gonadotropin/intrauterine insemination (IUI) cycles. This retrospective cohort study included a total of 964 patients undergoing 1926 gonadotropin/IUI cycles at an academic fertility center. Primary outcome measure was the association between serum AMH and measured ET on the day of and the day before human chorionic gonadotropin hormone (hCG) ovulation trigger. The effect of a model combining AMH and ET on early pregnancy outcomes was a secondary measure. In 52.8% of cycles, ET was last assessed and recorded on the day of hCG administration, while in the remaining 47.2% on the day prior to trigger. In unadjusted regression models, AMH was weakly correlated with ET on hCG trigger day [bAMH (95%CI) = 0.032 (- 0.008, 0.070), p = 0.015]. When adjusting for potential confounders, the positive correlation became significant [0.051 (0.006, 0.102), p = 0.047]. Similar findings were observed when assessing the correlation between AMH and ET on the day prior to hCG trigger. ET was non-significantly associated with the odds of clinical pregnancy, when adjusting for potential confounders, except for when restricting the analysis to couples with idiopathic infertility [OR (95%CI), p-value: 0.787 (0.623, 0.993), 0.044]. Our findings support an effect of serum AMH on endometrial development in gonadotropin induced cycles, even when adjusting for the diagnosis of PCOS. ET was not associated with the odds of achieving a clinical pregnancy, except for couples with idiopathic infertility.

Soft ovarian stimulation protocol in polycystic ovary syndromes women inspired by gonadotropin stimulated intrauterine insemination cycles converted to rescue IVF: time to shift the focus “retrospective study”

BackgroundPolycystic ovary syndrome (PCOs) women usually exhibit a high luteinizing hormone (LH) and hypersensitivity to exogenous gonadotropins stimulation which is a tremendous risk to ovarian hyperstimulation syndrome (OHSS). Since the pathophysiology of PCOS is mysterious, an aetiological approach to the treatment is difficult and should be individually designed. These features affect the outcome of treatment including ovulation and success rate. Also, PCOS women who have difficulty conceiving, frequently experience substantial treatment burden, risk, and psychological distress. Recently, a renewed interest has emerged in patient-friendly, low-risk, and less costly IVF treatments. Our study proposed a new soft protocol in PCOS ovrian stimulation without prior pituitary desensitization followed by fresh embryo transfer. Patients and methods: a retrospective cohort study was conducted between January 2018 to December 2021, including 48 out of 325 women with PCOS who underwent gonadotropin-stimulated intrauterine insemination cycles but due to unexpectedly high response with risk of multiple pregnancies and OHSS, they had been shifted to a rescue IVF and fresh embryo transfer. The primary outcomes were biochemical pregnancy, implantation rate, clinical pregnancy, rate of miscarriage, OHSS, and multiple pregnancies. Secondary outcomes were the endocrinological profiles, gonadotropin dose, and duration of stimulation. This study aims to evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to “rescue” in vitro fertilization (IVF/fresh embryo transfer) regarding implantation rates, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS).ResultsThis study used a low dose gonadotropin injections (2.1 ± 1.4) for an average duration of (9.1 ± 1.2) and showed a high success pregnancy rate: biochemical pregnancies (56.2%), implantation rate (50.2%), clinical pregnancy rate (49.9%), and miscarriage rate (8.5%). Multiple pregnancies occurred in (6.6%) and OHSS(4.4%) only in a mild form.ConclusionOur study revealed that ovarian stimulation without prior pituitary suppression in high responders was feasible to improve the implantation rate and alleviate profound OHSS without compromising the pregnancy outcomes. This encourages all fertility specialists to implement this new protocol with expected high responders as an alternative to the conventional cycle segmentation protocol: GnRH agonist-antagonist IVF/freeze-all strategy.

How to dose follitropin delta for the first insemination cycle according to the ESHRE and ASRM guidelines; a retrospective cohort study

BackgroundFollitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines.ResultsA retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6–9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0–4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0–6.0mcg FD.ConclusionsFollitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.

Live birth associated with peak serum estradiol levels in letrozole intrauterine insemination cycles

To identify whether the serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) trigger or luteinizing hormone (LH) surge (hCG-LH) was associated with the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI). Retrospective cohort study. Large, multicenter private practice. A total of 2,368 OI-IUI cycles in patients treated with letrozole followed by IUI were evaluated from January 1, 2014, to July 31,2019. Ovulation induction with letrozole, followed by autologous IUI. The primary outcome measure was the LBR as a function of the serum E2 level at the time of hCG administration or LH surge, adjusting for age, body mass index, the largest follicle diameter, and the number of follicles ≥14 mm in diameter. The clinical pregnancy rate as a function of the E2 level, pregnancy rate as a function of the lead follicle diameter, and pregnancy loss rates were the secondary outcome variables. A total of 2,368 cycles met the inclusion criteria. Outcomes were evaluated at the 25th (E2 level, 110 pg/mL), 50th (157 pg/mL), 75th (225 pg/mL), and 90th (319 pg/mL) percentiles. The LBRs ranged from 9.4% to 11.1% in the lower E2 cohorts and from 12.5% to 13.5% in the higher E2 cohorts. The LBR was significantly greater in the cohort of women with higher E2 levels in all percentile comparisons except for the 90th percentile. The mean periovulatory follicle diameter of ≥20 or <20 mm was not independently associated with the LBR or clinical pregnancy rate, despite a significantly higher mean E2 level in the larger follicle group. In letrozole OI cycles followed by IUI, lower LBRs and clinical pregnancy rates were found in women with lower E2 levels than in those with higher E2 levels at the 25th, 50th, and 75th percentile E2 level quartiles. Where possible, delaying hCG trigger until the E2 level increases after aromatase inhibition and approaches the physiologic periovulatory level may improve the pregnancy rates with letrozole followed by IUI.

Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders.

Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.

Correlation of progesterone level on the day of human chorionic gonadotropin injection in intrauterine insemination cycle and fertility rate

Background: Intrauterine insemination (IUI) is one of the assisted reproductive techniques widely used in infertility treatment. This must be done at a specific time, and progesterone plays an important role in the implantation process, a prerequisite for embryonic attachment and invasion. This study aimed to evaluate the relationship between progesterone levels on the day of human chorionic gonadotropin (hCG) injection in the IUI cycle and fertility. Methods: In this cross-sectional descriptive study, patients referred to the Infertility Center of Ardabil University of Medical Sciences for IUI during 2019-2020 were included. The pattern of the menstrual cycle, history of medical or surgical diseases, history of dyspareunia, number of previous IUIs, causes of infertility, and duration of infertility were entered in the relevant checklists. On the day of the hCG injection, a blood sample was taken, and the level of progesterone and estrogen were measured and evaluated. Results: A total of 85 patients were included in the study. The IUI result was negative in 67 (78.8%) patients. The mean total IUI history of patients was 1.71 ± 0.8 years. The mean duration of infertility was 35.11 ± 18.31 months. The highest fertility rate was observed in the serum level of 1.21-1.6 progesterone. The mean serum level of estradiol was 816.46 ± 651.00 months. Conclusion: The results of this study showed that the highest fertility rate was observed in the serum level of 1.21-1.6 progesterone in the IUI cycle.

Comparative Study of Dual Trigger vs hCG Trigger in Intrauterine Insemination Cycles

Comparative Study of Dual Trigger vs hCG Trigger in Intrauterine Insemination Cycles

Does luteal Phase Support with Vaginal Micronized Progesterone Effect on Pregnancy Rates in Intrauterine Insemination (IUI) Cycles in Two Infertility Center During Six-Year Follow-up?

Introduction: Husband artificial intrauterine insemination (IUI) is a standard method of assisted reproduction for patients with mild male infertility, anovulation, endometriosis, and unknown infertility. In this study, we evaluated the effect of luteal phase support on the success rate of IUI cycles with vaginal micronized progesterone compared to the control. Material and Methods: This retrospective cohort study included 94 infertile women referring to two infertility centers in Sari, Iran, from 2015 to 2021. In these women, Clomiphene citrate or Letrozole was used, follicular monitoring continued, and human Gonadotropin was added based on ultra-sonographic findings. Intramuscular HCG was added when one or two follicles were to 17 mm. IUI was done 36 hours later, and micronized vaginal progesterone 400mg once daily was added on the day after insemination (n=114). IUI outcomes were evaluated with a serum Beta-HCG test and vaginal ultrasound two and five weeks later. Pregnant women were followed up until the end of the pregnancy. Data were analyzed with SPSS25 and STATA14 software. Results: Progesterone consumption had no significant relationship with pregnancy rates but a significant correlation with the number of antral follicles. Pregnancy occurrence was significantly associated with patient satisfaction, FSH, and AMH levels but not correlated with the duration and kinds of infertility. Conclusion: Vaginal micronized progesterone as luteal phase support is not effective in increasing pregnancy occurrences in IUI cycles like IVF cycles, but patients’ satisfaction may be increased among women impregnated undergoing IUI and progesterone support.

Estimation of follicular growth—widely used, seldom studied

We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in intrauterine insemination (IUI) cycles. Patient and cycle characteristics were extracted from an existing database. Comparisons were made between the pregnant (defined as a positive beta hCG) and non-pregnant groups for the following variables: patient’s age, number of previous IUI cycles, type of ovarian stimulation, endometrial thickness, number of follicles measuring 14 mm and above, pre and post wash sperm parameters, cycle day when IUI was done and number of days between last ultrasound scan and ovulation trigger. A total of 7302 cycles were included in the final analysis. In 4055 cycles (55.5%) the hCG trigger was on the day of the last ultrasound, in 2285 cycles (31.3%) the hCG trigger was 1 day after the last ultrasound, in 850 (11.6%) it was 2 days after the last ultrasound and in 112 (1.5%) it was 3 or more days after the last ultrasound. Sperm parameters, younger maternal age, and the number of follicles above 14 mm were all associated with pregnancy. No association was found between positive pregnancy test rates and the time from last ultrasound to hCG trigger. Planning IUI based on the estimation of follicular growth 1–4 days before trigger, does not affect pregnancy rates.

The role of peak serum estradiol level in the prevention of multiple pregnancies in gonadotropin stimulated intrauterine insemination cycles

The objective was to assess whether the measurement of serum estradiol (E2) level on trigger day in controlled ovarian stimulation with intrauterine insemination (COS-IUI) cycles helps lower the multiple pregnancy (MP) rate. We performed a unicentric observational study. We included all patients who underwent COS-IUI and had a subsequent clinical pregnancy (CP) between 2011 and 2019. Our main outcome measure was the area under Receiver-Operating Characteristic (ROC) curve. We included 455 clinical pregnancies (CP) obtained from 3387 COS-IUI cycles: 418 singletons, 35 twins, and 2 triplets. The CP, MP, and live birth rates were respectively 13.4%, 8.1% and 10.8%. The area under ROC curve for peak serum E2 was 0.60 (0.52–0.69). The mean E2 level was comparable between singletons and MP (260.1 ± 156.1 pg/mL vs. 293.0 ± 133.4 pg/mL, p = 0.21, respectively). Univariate and multivariate logistic regression analysis showed that E2 level was not predictive of MP rate (aOR: 1.13 (0.93–1.37) and 1.06 (0.85–1.32), respectively). Our study shows that, when strict cancelation criteria based on the woman’s age and follicular response on ultrasound are applied, the measurement of peak serum E2 levels does not help reduce the risk of MP in COS-IUI cycles.

A Comparison of Triple and Double Sperm Washing for Density Gradient Preparation in Intrauterine Insemination Cycles when Overnight Incubation of Specimens Occurred: A Retrospective Cohort

Background: The number of sperm washes to maximize outcomes for intra-uterine insemination has not been well investigated. Therefore, we undertook to compare the pregnancy and live birth rates of triple sperm washing and double sperm washing for density gradient preparation for intrauterine insemination (IUI) cycles. Methods: A retrospective cohort study including 279 couples (136 couples with triple sperm washing and 143 couples with double sperm washing) with a diagnosis of unexplained infertility and mild male subfertility who had IUI cycles between April 2015 and April 2017 were evaluated. After overnight incubation of the sperm, subjects underwent either traditional double sperm washing or Triple sperm washing which consists of use of a third gradient and spinning procedure to the conventional double gradient sperm washing in order to obtain a higher quantity of motile sperm. Results: Total sperm count after triple washing was higher than double sperm washing (98.25 ± 62.06 vs. 81.08 ± 31.57; p = 0.003). Positive β-hCG test and live birth per cycle were higher in triple sperm washing (25.8% vs. 13.3%, p = 0.009; 18.4% vs. 9.8%, p = 0.039; respectively) than in the double sperm washing group. Conclusions: The use of motile sperms obtained from triple sperm washing may increase the rates of pregnancy and live birth in IUI cycles of women with unexplained and mild male factor infertility. A prospective randomized study should be undertaken to confirm the results.

Optimal lead follicle size in letrozole human menopausal gonadotrophin intrauterine insemination cycles with and without spontaneous LH surge

Research questionWhat is the optimal lead follicle size in letrozole, human menopausal gonadotrophin and intrauterine insemination (IUI) cycles with and without spontaneous LH surges? DesignThis retrospective cohort study included 3797 letrozole HMG IUI cycles between January 2010 and May 2021. All cycles were divided into two groups: the HCG trigger group (trigger day LH ≤15 mIU/ml) and the spontaneous LH surge group (trigger day LH >15 mIU/ml). These two groups were subdivided into smaller groups based on the diameter of the follicles. The primary outcome measure was clinical pregnancy rate. Logistic regression analysis was conducted to explore other risk factors. ResultsIn the HCG trigger group, the clinical pregnancy rate varied significantly, with rates of 20.8%, 14.9% and 11.8% for the 16.1–18.0, 18.1–20.0 and 20.1–22.0 mm groups, respectively (P = 0.005). In the spontaneous LH surge group, the pregnancy rate of follicles within 14.1–16.0 mm was significantly higher than that of follicles within 20.1–22.0 mm (adjusted OR 0.533, 95% CI 0.308 to 0.923, P = 0.025). Also, patients with two lead follicles were 2.569 times more likely to achieve a clinical pregnancy than those with only one lead follicle (adjusted OR 2.569, 95% CI 1.258 to 5.246, P = 0.010). The duration of infertility was also found to be a common influencing factor in both groups. ConclusionsThe optimal lead follicle size was between 16.1 and 18.0 mm in HCG-triggered letrozole HMG IUI cycles. If the lead follicle size is relatively small (14.1–18.0 mm) when a spontaneous LH surge occurs, there is no need to cancel the IUI cycle.

Optimizing pregnancy outcomes in intrauterine insemination cycles by stratifying pre-wash total motile count and patient-specific factors: a patient counseling tool.

The purpose of this study is to clarify which pre-wash total motile count are associated with improved clinical pregnancy rate (CPR) and live birth rate (LBR) based on maternal age, AMH level, stimulation regimen, and infertility diagnosis. This was a retrospective cohort study of first completed IUI cycles at two academic fertility centers from 5/2015 to 9/2019. Cycles were stratified by pre-wash TMC, maternal age, AMH level, stimulation regimen, and infertility diagnosis. The primary outcome was CPR and secondary outcomes were live birth and miscarriage. One thousand one hundred fifty-four cycles were analyzed. Of the 162 cycles that resulted in a CPR (14.0%), most had an insemination TMC > 20 million. Compared to TMC > 20 million, there was no difference in CPR or LBR for lower TMC categories, excluding the TMC < 2 million group, in which there were no pregnancies. When TMC was stratified by deciles, there was also no difference in CPR and LBR, including within the lowest decile (TMC 0.09-8.6 million). Younger age and higher ovarian reserve parameters were associated with higher pregnancy and LBR when stratified by TMC. There was no difference in pregnancy and LBR when considering different stimulation protocols. Our data suggest that pregnancy and LBR are equivalent above a TMC of 2 million. Data stratified by TMC and patient parameters can be used to counsel patients pursuing ART.

Analysis of the split insemination (IVF+ICSI) treatment in patients with borderline semen in first cycle

PurposeThe aim of this study was to verify the effectiveness of the split insemination (IVF+ICSI) in patients with borderline semen for the first cycle, we furthermore compared the treatment outcome of the conventional IVF and ICSI on sibling oocytes with the rate of blastocyst formation in different days (day 5 or day 6) as primary outcome and pregnancy as secondary outcome to provide theoretical support for embryo selection. MethodsBetween January 2017 and November 2021,190 couples undergoing the split insemination (IVF+ICSI) cycle were enrolled in the study with at least eight oocytes and the borderline semen in first cycle to analyze the basic characteristics and clinical outcome. The remaining 157 patients were analyzed in this study to compare the IVF and ICSI after excluding those who were completely unfertilized by IVF (n=33) including a patient who was completely unfertilized by IVF and ICSI. ResultsPresent study showed that about 32(32/190,16.8%) patients with borderline semen in first cycle were completely unfertilized performing the conventional IVF and only 1(1/190,0.53%) patient was completely unfertilized using the IVF and ICSI in the split insemination (IVF+ICSI), the rate of total fertilization failure (TFF) was significantly decrease by the ICSI treatment (16.8%&0.53%,P<0.0001).By the split oocytes, the fertilization rate was significantly superior in ICSI(729/982,74.2%) compared to IVF (486/940, 51.7%, P<0.0001), the usable blastocyst and high-quality blastocyst rate on the fifth day were statistically superior in IVF compared to ICSI(31.3% &22.8%,P=0.009) (27.3%&20.6%,P=0.03), The pregnancy rate, implantation rate and live birth rate in the IVF first cycle were higher than the ICSI(75.9%&64%, respectively) (52.3%&41.8%, respectively)(64.8%&54.7%, respectively),although there was no statistical difference,it is also about ten percentage points difference. ConclusionsThe treatment of sibling oocyte with both IVF and ICSI could be an appropriate choice to prevent TFF and preserve the embryo development potential for the patients with the borderline semen in present study. Furthermore, the embryo development potential from conventional IVF was better than the embryo from the ICSI technology, the ICSI technology may have a negative effect on the embryo development.

Effect of inactivated COVID-19 vaccination on intrauterine insemination cycle success: A retrospective cohort study.

BackgroundVaccine hesitancy was found in couples seeking artificial reproductive technology (ART) services. As the main vaccine used in China, investigations into the influence of inactivated coronavirus disease 2019 (COVID-19) vaccines on human fertility is needed.MethodsThis retrospective cohort study included data on COVID-19 vaccination, clinical characteristics, and reproductive outcome of 1,000 intrauterine insemination (IUI) cycles in 653 couples from March 2021 to March 2022 in a single university hospital-based center for reproductive medicine. The IUI cycles were divided into two categories based on sperm source, including 725 cycles in 492 women undergoing artificial insemination with their husband's sperm (AIH) and 275 cycles in 161 women undergoing artificial insemination with donor sperm (AID). Women were then divided into two groups. The vaccine exposed group included women vaccinated prior to insemination and the unexposed group included women who were not vaccinated or vaccinated after insemination. Reproductive outcomes including ongoing pregnancy rate, clinical pregnancy rate, and miscarriage rate were assessed.ResultsInactivated COVID-19 vaccinated women prior to intrauterine insemination in AIH cycles have comparable ongoing pregnancy rate (11.1 vs. 10.3%, P = 0.73), clinical pregnancy rate (12.5 vs. 11.3%, P = 0.60) as compared with unvaccinated counterparts. Similarly, there were no significant differences in ongoing pregnancy rate (20.9 vs. 28.1%, P = 0.17), clinical pregnancy rate (21.7 vs. 28.8%, P = 0.19) between vaccine exposed and unexposed groups in AID cycles. Multivariable logistic regression analyses showed that inactivated COVID-19 vaccination status cannot independently influence the reproductive outcomes of AIH and AID cycles. Subgroup analysis of vaccine exposed cycles showed that doses of vaccination and Interval between the last dose of vaccination and insemination have no influence on the reproductive outcomes of AIH cycles.ConclusionsNo negative effects were found on female fertility in IUI cycles following exposure to the inactivated COVID-19 vaccine. These findings indirectly reflect the safety of inactivated COVID-19 vaccine toward reproductive health and help to mitigate vaccine hesitancy among people planning to conceive.

Impact of recurrent pregnancy loss history on reproductive outcomes in women undergoing fertility treatment

Recurrent pregnancy loss negatively affects the reproductive outcomes of natural conception. Preimplantation genetic testing for aneuploidies has been the focus of interventions in women with recurrent pregnancy loss. However, the risk of no embryos being available, high costs, and uncertainties surrounding its effectiveness limit its use. Factors beyond euploidy, such as an appropriate intrauterine environment, are also important for improving the reproductive outcomes in women with recurrent pregnancy loss. It remains unknown whether a history of recurrent pregnancy loss can affect reproductive outcomes after fertility treatment. This study aimed to investigate the impact of history of recurrent pregnancy loss on the reproductive outcomes of women undergoing fertility treatment. This was a retrospective cohort study of women who underwent their first frozen embryo transfer cycle or intrauterine insemination cycle between January 2014 and July 2020 in Shanghai, China. We excluded couples with known karyotypic abnormalities (eg, balanced translocation) or uterine malformation. We performed multivariate binary logistic regressions for biochemical pregnancy, miscarriage, and live birth rates to investigate the associations between recurrent pregnancy loss history and reproductive outcomes. A total of 29,825 women who underwent frozen embryo transfer cycles and 5476 women who underwent intrauterine insemination cycles were included in this study. In those who underwent frozen embryo transfer, history of recurrent pregnancy loss was not significantly associated with biochemical pregnancy (adjusted odds ratio, 1.19; 95% confidence interval, 0.87-1.63), miscarriage (adjusted odds ratio, 0.99; 95% confidence interval, 0.78-1.26), or live birth rates (adjusted odds ratio, 0.91; 95% confidence interval, 0.79-1.06). Similarly, in frozen embryo transfer cycles that led to clinical pregnancy, recurrent pregnancy loss history was not significantly associated with live birth (adjusted odds ratio, 0.99; 95% confidence interval, 0.76-1.28) or miscarriage rates (adjusted odds ratio, 1.04; 95% confidence interval, 0.81-1.35). In women with intrauterine insemination, history of recurrent pregnancy loss showed no significant associations with fertility outcomes in all cycles ([adjusted odds ratio, 1.36; 95% confidence interval, 0.88-2.10] for live birth rate and [adjusted odds ratio, 1.74; 95% confidence interval, 0.75-4.01], for miscarriage rate) and in cycles that led to clinical pregnancy ([adjusted odds ratio, 0.70; 95% confidence interval, 0.31-1.63] for live birth rate and [adjusted odds ratio, 1.45; 95% confidence interval, 0.58-3.63] for miscarriage rate). In women without obvious chromosome abnormality and uterine malformation who undergo fertility treatment, recurrent pregnancy loss history was not significantly associated with miscarriage and live birth rates, suggesting that it has little or no prognostic value in predicting the reproductive outcomes of frozen embryo transfer or intrauterine insemination cycles.

P-116 Clinical predictors of live birth rate (LBR) in donor-intrauterine insemination (D-IUI) cycles

Abstract Study question Which clinical parameters can predict LBR in D-IUI cycles? Summary answer Only age returned as a clinical predictor of D-IUI LBR. Total motile sperm count for insemination (TMSC) and stimulation protocol may help clinicians optimise LBR. What is known already D-IUI cycles are a popular treatment option for patients requiring male gamete donation. For both patient and clinician, identification of parameters that can guide clinical decision-making during fertility treatment is important to optimise clinical outcomes. To date, few studies have investigated D-IUI cycle parameters with live birth as the primary outcome. Moreover, previous studies can be limited from lack of control of covariates, as well not accounting for data skewing from inclusion of multiple cycles per patient. Study design, size, duration A retrospective analysis of 1925 D-IUI cycles in 638 patients between 2018-2020 at a single UK-based centre was performed. All donors were recruited by the London Sperm Bank as per the HFEA regulations. Inclusion criteria for donor sperm quality were all samples that met the WHO criteria. Exclusion criteria were cycles where live birth outcome was unknown. Participants/materials, setting, methods Patients underwent natural or stimulation cycle. Stimulation included clomiphene or letrozole, gonadotrophins +/- GnRH agonist, an hCG trigger or LH-monitoring to time insemination and micronised vaginal progesterone for luteal support. Insemination was scheduled 24 hours following surge detection/trigger administration. TMSC is presented per 0.5ml vial, which is post-preparation sample for insemination. T-test for continuous variables and Fisher’s Exact test for categorical variables were performed. For multivariate analysis, a generalised mixed effects logistic regression was performed. Main results and the role of chance Median cohort age was 36 ± SE 0.1, median TMSC was 14x106 ± SE 0.2x106. Of recipients, 53% were same sex couples, 41% were single women, 6.3% were heterosexual couples. There was no significant difference in TMSCs between cycles that produced a live birth and those that did not (14x106 and 13.9x106 respectively, P = 0.1). Dividing TMSC into 5x106 increments demonstrated that small increases in LBR per cycle occurred between 2.5-25x106. On average, LBR increased by 1.3% with each increment up to 25x106, reaching 15%. Beyond this, no further increase in LBR was observed. However, these incremental increases were not statistically significant (P = 0.6). Gonadotrophin stimulation (without agonist) achieved significantly higher LBRs than all other protocols (17.1%, P &amp;lt; 0.001). This persisted when stratifying by age (&amp;lt;35; 30%, 35-37; 29%, 38+; 12.6%). A mixed effects logistic regression model demonstrated that only age returned as a significant negative predictor of LBR (aOR 0.9, 95% CI 0.86-0.94, P &amp;lt; 0.001). There was no effect of TMSC on LBR (aOR 1.0, 95% CI 0.99-1.02, P = 0.7). Gonadotropin stimulation was associated with over double increased odds of achieving a live birth, which came close to significance (aOR 2.29, 95% CI 0.98-5.4, P = 0.06). Limitations, reasons for caution The choice of management regimen could have been influenced by uncontrolled factors, introducing bias in this retrospective study. Other semen parameters were not included in the multivariate analyses which could, in turn, have affected live birth outcome, which should be considered. Wider implications of the findings These findings demonstrate that increasing TMSC may be associated with small rises in LBR up to 25x106 in D-IUI cycles. While gonadotrophin stimulation appeared most effective, only age was shown to be an independent predictor of LBR. Collectively, these parameters may assist clinicians in optimising LBR in D-IUI cycles. Trial registration number None

P-588 Evaluation of anti-Müllerian hormone levels as a predictor of pregnancy outcome following intrauterine insemination in infertile women

Abstract Study question Is a low anti-Müllerian hormone (AMH) level (&amp;lt;1.0 ng/mL) negatively associated with pregnancy outcomes in intrauterine insemination (IUI) cycles? Summary answer Clinical pregnancy, spontaneous abortion, and ongoing pregnancy rates are comparable between patients with AMH levels &amp;lt;1.0 and ≥1.0 in all age categories. What is known already Before ovarian stimulation for IVF treatment is recommended, many patients will first be treated with ovulation induction and IUI. Compared to IVF, intrauterine insemination has acceptable success rates, fewer risks, and is less expensive. However, in patients with diminished ovarian reserve, clinicians may be inclined to recommend that a patient proceed straight to IVF due to a concern that IUI cycles may yield unacceptable pregnancy and live birth rates, and that these cycles may waste valuable time for the patient. Study design, size, duration This was a retrospective cohort study of infertile patients at an academic center. The first ovulation induction/IUI cycle with oral medication (clomiphene or letrozole) between 2015-2019 was included. Patients that did not have an AMH level within 12 months of the treatment cycle were excluded. Spontaneous abortion was defined as the spontaneous demise of an intrauterine fetus before 8 weeks’ gestation. Ongoing pregnancy was defined as a viable intrauterine fetus at 8 weeks’ gestation. Participants/materials, setting, methods The primary outcome was ongoing pregnancy. Patients were stratified into two groups based on their AMH level: Group 1 (AMH &amp;lt;1.0; n = 606) and Group 2 (AMH ≥1.0; n = 2518). Patients were further categorized by age to control for the association between age and low AMH level (&amp;lt;35 years, 35-40 years, and &amp;gt;40 years). Modified Poisson regression model with robust error variance adjusted a priori for patient age was used to estimate the RR (95% CI). Main results and the role of chance The mean age of patients with an AMH &amp;lt;1.0 was 38.8 ± 3.8 years and with an AMH ≥1.0 was 35.2 ± 3.8 years. The mean AMH level of patients with an AMH &amp;lt;1.0 was 0.6 ± 0.3 ng/mL and with an AMH ≥1.0 was 4.6 ± 4.7 ng/mL. Additional demographics including body mass index, race, use of clomiphene versus letrozole, number of follicles ≥14mm at trigger, endometrial thickness, and post-wash total motile sperm count were comparable between the two groups. Among the entire cohort, when patients with an AMH &amp;lt;1.0 were compared to patients with an AMH ≥1.0, after adjusting for age, there were no significant differences in clinical pregnancy (11.6% versus 15.0%; RR 0.90 (0.70-1.17)), spontaneous abortion (2.6% versus 2.1%; RR 1.29 (0.71-2.32)), or ongoing pregnancy rates (8.9% versus 12.9%; RR 0.83 (0.62-1.11)). Similarly, when patients were stratified into age groups, there were no significant differences in any pregnancy outcomes with an ongoing pregnancy rate: for patients &amp;lt;35 years (12.9% versus 15.0%; RR 0.84 (0.49-1.45), for patients 35-40 years (10.9% versus 12.1%; RR 0.95 (0.66-1.35)), and for patients &amp;gt;40 years (3.3% versus 4.5%; RR 0.89 (0.32-2.45). Limitations, reasons for caution As this was a retrospective study, selection bias is possible given that treatment decisions could not be prospectively controlled. However, we attempted to control for this in the study design by restricting our analysis to the first initiated cycle per patient and by excluding natural cycle and gonadotropin treatment cycles. Wider implications of the findings Our observations provide reassurance that a low AMH level is not associated with the chance of success or failure in an ovulation induction/IUI. Ovulation induction/IUI is, therefore, a reasonable option to consider before proceeding to IVF in patients with an AMH level &amp;lt;1.0 ng/mL. Trial registration number not applicable

O-246 A drop in serum progesterone(P4) levels between 5th and 7th days of triggering ovulation is associated with lower ongoing pregnancy rate(OPR) in intrauterine insemination cycles

Abstract Study question Is there any association between early- and mid-luteal phase serum P4 levels and OPR in patients undergoing IUI due to unexplained or mild male-factor infertility? Summary answer A drop in serum progesterone (P4) levels between 5th and 7th day of triggering ovulation is independently associated with lower OPR in IUI cycles. What is known already The definition of luteal phase insufficiency in natural cycles is controversial and might be encountered ∼10% of infertile couples. Serum P4 level measurement is a still the most feasible method for luteal phase monitoring. Recently, some research groups have been focusing on monitoring luteal phase in in-vitro fertilization cycles, however, there is scarce of evidence on luteal phase characteristics and reproductive outcomes in IUI cycles. Study design, size, duration A prospective cohort study. A total of 179 consecutive patients (230 cycles) with unexplained and mild male factor infertility undergoing IUI treatment at Hacettepe University in between June 2020 and May 2021 were included. For ovarian stimulation, of the included 230 cycles, clomiphene citrate and gonadotropin were used consecutively in 161 cycles and only gonadotropin in the remaining 69 cycles. The primary outcome measure was the OPR. No progesterone was administered for luteal phase support. Participants/materials, setting, methods Serum P4 levels were measured on the 5th and 7th day of hCG triggering.P4 level were available in 183 cycles for hCG+5 day, in 161 cycles for hCG+7 day. In order to investigate the effect of P4 levels on OPR, patients were divided into two groups as ≤ 10th percentile and &amp;gt;10th percentile according to serum P4 levels measured on hCG+5 and hCG+7 days, with the cut off values ≤5.6 ng/ml and ≤8.46 ng/ml, respectively. Main results and the role of chance Of the 230 cycles 17 (7.4%) were resulted with ongoing pregnancy. In the univariate analysis, the OPRs of the hCG+5 and hCG+7 serum P4 ≤10% and &amp;gt;10% groups were 10.5% (2/19) versus 5.5% (9/164) (p = 0.80) and 0% (0/16) versus 7.5% (n = 11/145) (p = 0.24), respectively. There was no ongoing pregnancy in patient with ≤8.46 ng/ml serum P4 level on hCG+7 day. The ΔP4 value was calculated by subtracting the serum P4 level measured on hCG+5 from the serum P4 level measured on day hCG+7 (ΔP4= hCG+7 – hCG+5). While none of the 26 patients with negative ΔP4 had ongoing pregnancy, 8 (6.2%) of 130 patients with positive ΔP4 had ongoing pregnancy (p = 0.194). In the multivariate-GEE (generalized estimating equation) analysis, ΔP4 was found to be an independent predictor of ongoing pregnancy alone (ß:0.137, 95% CI = 0.020-0.254, p = 0.02). Limitations, reasons for caution The physiological circadian pulsatile secretion of P4 during the mid-luteal phase and limited sample size are limitations, however, blood sampling was standardized to reduce the impact of timing. Wider implications of the findings Low progesterone level with the threshold ≤8.46 ng/ml on the hCG+7 day is associated lower OPR. Two measurements (hCG+5 day, hCG+7 day) of P4may delineate those patients with a drop in P4, associated lower OPRs. Rescuing these IUI cycles with additional P4supplementation should be tested in future randomized controlled trials. Trial registration number NCT04707430