AFFORDABLE IVF: DETERMINANTS OF LIVE BIRTH OR ONGOING PREGNANCY AFTER FIRST CYCLE OF LETROZOLE (LTZ) – GONADOTROPIN (GN) MILD STIMULATION, IMMEDIATE ICSI, AND INTRAVAGINAL EMBRYO CULTURE

Abstract

To determine what patient and cycle factors are associated with a favorable outcome when mild ovarian stimulation and immediate ICSI are combined with intravaginal embryo culture. Observational cohort of all 252 women with their first cycle start on this protocol in our practice from 6/2018 to 12/2019 who planned fresh transfer, comprising nearly all our first ART cycles. Later patient cycles were censored for lack of 24-week follow-up. Ongoing pregnancy (24+ weeks’ gestation) or live birth (OP/LB) was modeled by logistic regression. Women were non-tobacco users with BMI <40 kg/m2. LTZ x5 days was started 4 d after oral contraceptives were stopped, then overlapped on its 5th day with customized dose gonadotropins. No GnRH analogs were used. Cycle monitoring was repeated if necessary before hCG trigger; retrieval was 35 hr later under mild sedation in a hospital office. Metaphase (M) oocytes were immediately treated by ICSI and placed with media into an INVOcell (INVO Biosciences, Sarasota, FL), which was secured in the upper vagina by a diaphragm. Typically after 5 days, if available 1-2 blastocysts (blasts) were transferred. We modeled OP/LB according to patient and stimulation factors and oocyte and embryo outcomes using JMP Pro 12.0.1 (SAS Institute, NC). Mean female age was 34.2 (±4.6) yr; 25% had AMH <1.0 ng/mL, 67% were nulliparous, and 42% had prior pregnancy loss(es). Stimulations used 5–10 mg/day LTZ (5 mg in 69%) plus 1000 ± 500 units FSH over a median of 4 days (range 1-9). Only one follicle scan was done in 79%. Cancellation rate was 15%. Retrievals successfully obtained M-stage oocytes in 93% (M-2 in 78%), with a mean of 1.9 M-2's and 1.3 M-1's. Transfer [of blast(s)] followed 82% [60%] of 202 successful retrievals, with 93% of transfers on Day 5. There were 47 pregnancies ongoing or resulting in live birth. By univariable regression, factors associated (p<0.05) with OP/LB included age (odds ratio [OR] 0.92/yr; 95% confidence interval [CI] 0.85–0.98); total number of metaphase (M) oocytes (OR 1.24; 95% CI 1.08–1.42) and M-2 oocytes (OR 1.50; 95% CI 1.24–1.84) retrieved; and number of blasts obtained (OR 2.47; 95% CI 1.67–3.81). LTZ at 10 mg/d and higher daily GN dose were each negatively associated with OP/LB. No association of OP/LB was found with serum AMH, (nulli)parity, prior pregnancy loss, M-1 oocytes retrieved, or transfer of 2 vs. 1 blast. A non-significant negative trend was found for association of OP/LB with cycle-day-3 E2 (p=0.08) and total GN dose (p=0.09), and a positive trend with number of embryos transferred (p=0.07). After adjustment for M-2 oocyte number, LTZ dose (p<0.01) and total GN dose (p<0.015) were each negatively associated with OP/LB; age retained borderline significance (p=0.07). Our lower-cost ART protocol, with LTZ-based mild stimulation, few monitoring visits, and intravaginal embryo culture, is more successful in younger women. M-2 oocyte yield and blast formation are predictive for successful pregnancy, but transfer of a second blast did not improve outcome. Higher LTZ and GN doses as employed were not associated with greater success.