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Updated: Nov 4, 2025
Fertility Preservation Through Oocyte Vitrification: Clinical and Laboratory Perspectives
Published on: September 16, 2021
Low dose hCG supplementation in a Gn-RH-agonist trigger protocol is associated with worse pregnancy outcomes: a
Maren Shapiro1,2, Phillip Romanski3,4, Ann Thomas3
1Obstetrics & Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. maren.shapiro@ucsf.edu.
Insights
A dual trigger using low-dose hCG with GnRH agonist (GnRHa) resulted in fewer live births and pregnancies compared to hCG alone, despite better stimulation. Subsequent frozen cycles showed comparable pregnancy rates, suggesting inadequate luteal support with the low-dose dual trigger.
Area of Science:
- Reproductive Endocrinology
- In Vitro Fertilization
- Ovarian Stimulation Protocols
Background:
- Ovarian hyperstimulation syndrome (OHSS) and pregnancy rates are key concerns in assisted reproduction.
- Dual trigger protocols combining human chorionic gonadotropin (hCG) and GnRH agonist (GnRHa) are used for oocyte maturation.
- Optimal hCG dosage in dual trigger regimens requires further investigation to balance OHSS risk and efficacy.
Purpose of the Study:
- To compare pregnancy and OHSS rates between dual trigger (low-dose hCG/GnRHa) and hCG-alone triggers.
- To evaluate pregnancy outcomes in subsequent frozen embryo transfer cycles.
- To determine the optimal hCG dose for dual trigger protocols in IVF.
Main Methods:
- Retrospective cohort study of 963 women (<41 years, BMI 18-40 kg/m², AMH >2 ng/mL) undergoing IVF with GnRH antagonist protocol.
- Comparison between a low-dose dual trigger group (1000u hCG + 2mg GnRHa) and an hCG-alone group (10,000u hCG).
- Analysis of implantation, pregnancy, live birth, and OHSS rates, as well as frozen cycle outcomes.
Main Results:
- The dual trigger group exhibited younger age, higher AMH, more oocytes retrieved, and higher fertilization rates.
- Clinical pregnancy (43.4% vs 52.8%) and live birth (33.4% vs 45.8%) rates were significantly lower in the dual trigger group.
- Three cases of OHSS occurred exclusively in the hCG-only group; frozen cycle pregnancy rates were similar between groups.
Conclusions:
- Dual trigger with low-dose hCG (1000u) showed poorer pregnancy outcomes despite favorable patient characteristics and stimulation parameters.
- Inadequate luteal phase support from the low-dose hCG in the dual trigger is hypothesized as the cause.
- Subsequent frozen cycles achieving comparable pregnancy rates support the luteal phase support hypothesis, leading to a protocol adjustment to 1500u hCG in dual triggers.
Background:
A number of studies have looked at dual triggers with hCG and GnRH agonist (GnRHa) in varying doses, but the question remains: what is the optimal dose of hCG to minimize ovarian hyperstimulation syndrome (OHSS) and still offer adequate pregnancy rates? The purpose of this study was to compare pregnancy and OHSS rates following dual trigger for oocyte maturation with GnRHa and a low-dose hCG versus hCG alone. A secondary objective was the assess pregnancy outcomes in subsequent frozen cycles for the same population.
Methods:
A total of 963 women < 41 years old, with a BMI 18-40 kg/m2 and an AMH > 2 ng/mL who underwent fresh autologous in vitro fertilization (IVF) with GnRH antagonist protocol at a University-based fertility center were included in this retrospective cohort study. Those who received a low dose dual trigger with hCG (1000u) and GnRHa (2 mg) were compared to those who received hCG alone (10,000u hCG/250-500 μg Ovidrel). Differences in implantation rates, pregnancy, live birth, and OHSS were investigated.
Results:
The dual trigger group was younger (mean 33.6 vs 34.1 years), had a higher AMH (6.3 vs 4.9 ng/mL,) more oocytes retrieved (18.1 vs 14.9) and a higher fertilized oocyte rate (80% vs 77%) compared with the hCG only group. Yet, the dual trigger group had a lower probability of clinical pregnancy (gestational sac, 43.4% vs 52.8%) and live birth (33.4% vs 45.8%), all of which were statistically significant. There were 3 cases of OHSS, all in the hCG-only trigger group. In subsequent frozen cycles, pregnancy rates were comparable between the two groups.
Conclusions:
The dual trigger group had a better prognosis based on age and AMH levels and had better stimulation outcomes, but significantly worse pregnancy outcomes, suggesting the low dose hCG (1000u) in the dual trigger may not have provided adequate luteal support, compared to an hCG-only trigger (10,000u hCG/250-500 μg Ovidrel). Interestingly, the pregnancy rates were comparable in subsequent frozen cycles, further supporting the hypothesis that the issue lies in inadequate luteal phase support, rather than embryo quality. Based on these findings, our program has changed the protocol to 1500u of hCG in a dual trigger.
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