Ovulation Induction Intrauterine Insemination: Predictors of Success
Citation
Lu, Yao. 2022. Ovulation Induction Intrauterine Insemination: Predictors of Success. Master's thesis, Harvard Medical School.Abstract
Project 1Abstract
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 and those who did not while using CC. Furthermore, we evaluated the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles.
Design: Retrospective study.
Setting: Academic fertility center.
Patients: To evaluate CC’s impact on the endometrium, utilizing women as their own controls, we included in cohort 1 all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307). Furthermore, to evaluate EMT differences between patients who conceived with CC and those who did not, all CC/IUI cycles from women who eventually conceived with CC during the same study period were included in cohort 2 (CC2, n=686).
Intervention(s): CC/IUI or Gn/IUI.
Outcome Measure(s):
Primary: EMT.
Secondary: Clinical pregnancy and spontaneous abortion rates (CPR, and SABR, respectively).
Statistics: CC1 cycles were compared to both Gn1, and CC2 cycles in regards to EMT. In cohort 1, CC1 and Gn1 cycles from the same patient were matched to estimate the within-patient variability of EMT. Generalized linear mixed models (GLMM) and generalized estimating equations (GEE) models were applied to account for multiple cycles from the same patient while controlling for confounders, as appropriate.
Results: When CC1 was compared to Gn1 cycles, EMT was significantly thinner [Median (IQR): 6.8 (5.5-8.0) vs. 8.3 (7.0-10.0) mm, p.001]. Within-patient, CC1 compared to Gn1 EMT was on average (mean±SD): 1.7±2.1 mm [median (IQR): 1.6 (0.5, 3.0) mm] thinner. GLMM models, adjusted for confounders, revealed similar results (coefficient: 1.69, 95% CI: 1.52-1.85, CC1 as ref.).
CC1 compared to CC2 EMT was also thinner both before [Median (IQR): 6.8 (5.5-8.0) vs. 7.2 (6.0-8.9), respectively, p.001] and after adjustment in GLMM models (coefficient: 0.59, 95% CI: 0.34-0.85, CC1 as ref.).
CPRs improved as EMT quartiles increased among CC cycles (p.001), while no such improvement was observed among Gn cycles (p=0.94). GEE models, adjusted for cofounders, suggested a positive association between EMT and CPR in CC cycles (adjOR: 1.12, 95% CI: 1.07-1.18, p.001) but not in Gn cycles (adjOR: 0.99, 95% CI: 0.92-1.07, p=0.82).
Conclusions: Within-patient, overall CC resulted in thinner EMT compared to Gn. Patients who failed to conceive with CC also had a thinner endometrium compared to those who eventually conceived with CC. Thinner endometrium was associated with decreased CPR in CC cycles, while no such association was detected in Gn cycles.
Keywords: endometrial thickness, ovarian stimulation, clomiphene, gonadotropin, intrauterine insemination
Project 2
Abstract
Objective: To investigate the effectiveness of intrauterine insemination (IUI) for women with “overt” tubal factor (TF) infertility or “subtle” TF, such as those with endometriosis, in comparison to those with unexplained infertility.
Design: Retrospective cohort study.
Setting: Academic fertility center.
Patients: Women who underwent IUI cycles due to tubal factor infertility (TF, 269 cycles from 105 women), endometriosis (ENDO, 242 cycles from 87 women), or unexplained infertility (UE, 4102 cycles from 1433 women) between January 2004 and October 2021 were included.
Intervention(s): IUI with or without ovarian stimulation (OS).
Main Outcome Measure(s): The primary outcome was ongoing pregnancy rate (OPR). Secondary outcomes included positive HCG rate, clinical, multiple, and ectopic pregnancy rates, as well as rate of spontaneous abortion (CPR, MPR, EcPR, and SABR, respectively).
Results: While CPRs were similar among the three groups (TF: 10.0%, ENDO: 10.3%, and UE: 12.6%, p=0.30 for all comparisons), TF had 8.17 times the risk for EcPR compared to UE group (TF: 11.1% vs. UE: 1.4%, p=0.01; RR: 8.17, 95% CI: 2.24-29.87, UE: ref.). While OPRs per initiated cycle were comparable (p=0.12), OPRs per identified clinical pregnancy were lowest among patients with TF (TF: 63.0%, ENDO: 92.0%, UE: 80.8%, p=0.03 for all comparisons). After adjusting for age, BMI, basal FSH, prior parity, OS regimen, and total progressive motile sperm count, results showed that cycles in TF group had a 47% lower chance for ongoing pregnancy compared to those with UE (adjOR: 0.53, 95% CI: 0.31-0.91, p=0.02), while no such association was observed in ENDO compared to UE. Interestingly, although cumulative OPRs after 3 or 4 IUI cycles were lowest in TF group, the differences among groups did not reach statistical significance (p=0.18 and 0.08, for 3 and 4 cycles, respectively).
Conclusions:
Overt tubal factor infertility seemed to be associated with impaired IUI outcomes with regard to increased EcPR and decreased OPR as compared to unexplained infertility, whereas our results do not suggest such associations for women “at-risk” for TF such as those with endometriosis.
Keywords: intrauterine insemination, tubal factor, endometriosis, unexplained infertility, pregnancy outcome
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