Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles

Abstract

ObjectiveTo evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity.DesignRetrospective cohort.SettingAcademic medical center.PatientsFresh IVF cycles from 9/2004–12/2011.Intervention10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI.Main outcome measuresOocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose.ResultsPost-trigger serum b-hCG 20–30, 30–40, and 40–50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20–50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41–0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles.ConclusionsModerate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity.

Gonadotropin levels at the start of ovarian stimulation predict normal fertilization after hCG re‐trigger in GnRH antagonist cycles

“…In such cases, strategies to prevent the development of OHSS may include lower dose of hCG or cabergoline administration. There are various reports regarding the effect of low dose of hCG, 28,29 and Gunnala et al reported that a single administration of low‐dose hCG (3300 IU, similar to our study) can minimize the incidence of OHSS and facilitate oocyte maturity 30 . Esinler et al reported that cabergoline administration is a very effective way to reduce the risk of OHSS 31 .…”

The rate of euploid miscarriage is increased in the setting of adenomyosis

“…However, Day 16 post-ovulation serum βhCG levels in the adenomyosis group were significantly lower than those seen in the non-adenomyosis group (478.1 ± 686 vs 591 ± 543 IU/L, respectively; P = 0.0127), while serum progesterone levels were not significantly different (102.5 ± 112 vs 89.1 ± 58, P = 0.1895) (Supplementary Table SI). As obesity is known to lower serum βhCG levels, possibly due to a greater maternal volume of distribution (Gunnala et al , 2017), we performed a regression analysis controlling for the impact of maternal BMI. Importantly, this analysis still confirmed a statistically significant lower βhCG levels in the adenomyosis group at 4 weeks gestation independent of BMI.…”

Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment

“…In 2017, Gunnala et al ( 103 ) retrospectively reviewed 10,427 IVF/intracytoplasmic sperm injection (ICSI) cycles in which uhCG was administered at varying doses based on serum estradiol on the day of trigger (10,000 IU when estradiol was <1500 pg/mL; 5000 IU when estradiol was 1501 to 2500pg/mL; 4000 IU was estradiol 2501 to 3000pg/mL; and 3300 IU or dual trigger leuprolide 2 mg with 1500 IU of hCG when estradiol was >3000 pg/mL). The number of mature oocytes retrieved, fertilization rate, and number of embryos transferred did not differ by dose of hCG administered ( 103 ). However, estradiol levels on the day of trigger correlate with the number of follicles available to provide a mature oocyte, and thus higher doses of hCG could have been administered in patients with fewer follicles and fewer anticipated oocytes had the same dose been used.…”

“…However, estradiol levels on the day of trigger correlate with the number of follicles available to provide a mature oocyte, and thus higher doses of hCG could have been administered in patients with fewer follicles and fewer anticipated oocytes had the same dose been used. Oocyte maturation rate (proportion of oocytes retrieved that were mature) varied by serum level of hCG on the morning after administration (68% when hCG was 20 to 30 IU/L, 71% when hCG was 30 to 40 IU/L, 73% when hCG was 40 to 50 IU/L, and 79% when hCG was >50 IU/L; P < 0.05) ( 103 ). The same group analyzed 18,666 patients with serum β hCG levels ≥50 mU/mL and 418 patients with serum β hCG levels <50 mU/L on the day following hCG trigger and found that patients with a BMI ≥30 kg/m 2 had a 21-fold increased risk of having low serum β hCG level <50 mU/L ( 104 ).…”