Analysis of Related Factors Affecting Cumulative Live Birth Rates of the First Ovarian Hyperstimulation In Vitro Fertilization or Intracytoplasmic Sperm Injection Cycle: A Population-Based Study from 17,978 Women in China
Introduction
The evaluation of success in assisted reproductive technology (ART) remains a topic of debate, with growing consensus that cumulative live birth rate (CLBR) per complete ovarian stimulation cycle is a critical metric. This study focuses on analyzing CLBR following the first controlled ovarian hyperstimulation (COH) cycle for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in a large Chinese population. The aim is to identify key prognostic factors influencing CLBR, guiding clinical decision-making and patient counseling.
Study Design and Methods
This retrospective cohort study included 17,978 women undergoing their first IVF/ICSI cycles at Peking University Third Hospital between January 2013 and December 2014. Follow-up spanned four years, concluding in December 2018, to track outcomes from fresh and frozen embryo transfers (FET). Exclusion criteria included prior ART cycles, natural IVF/ICSI, and cycles for fertility preservation or genetic testing.
COH protocols varied, including long, short, ultralong, and antagonist protocols. Ovarian stimulation utilized recombinant follicle-stimulating hormone (rFSH), human menopausal gonadotropin (HMG), or a combination. Triggering with recombinant human chorionic gonadotropin (r-hCG) occurred when leading follicles reached ≥18 mm. Embryos were assessed using standard criteria, with surplus viable embryos vitrified for FET. Luteal phase support was standardized.
Outcome Measures
CLBR was defined as the proportion of live births achieved per initial ovarian stimulation cycle, incorporating all subsequent FET cycles. Statistical analyses used logistic regression to assess factors influencing CLBR, with significance set at P < 0.05.
Key Findings
The overall CLBR after the first COH cycle was 49.66% (8,928/17,978), with a cumulative pregnancy rate of 58.14%. Significant differences emerged between the live birth and non-live birth groups in demographics and treatment parameters:
- Age: Women in the live birth group were younger (30.81 ± 4.05 vs. 33.09 ± 5.13 years, P < 0.001).
- BMI: Lower BMI favored live birth (22.33 ± 3.35 vs. 22.75 ± 3.61 kg/m², P < 0.001).
- Infertility Duration: Shorter duration correlated with success (4.22 ± 3.11 vs. 5.06 ± 4.08 years, P < 0.001).
- Ovarian Response: Higher oocyte retrieval (15.35 ± 7.98 vs. 11.35 ± 7.60) and transferrable embryos (6.66 ± 5.19 vs. 3.62 ± 3.51, P < 0.001) improved outcomes.
Impact of Oocyte Yield on CLBR
Oocyte retrieval quantity strongly influenced CLBR (Figure 2):
- ≤5 oocytes: CLBR = 21.89%
- 6–10 oocytes: CLBR = 43.09%
- 11–15 oocytes: CLBR = 56.18%
- 16–20 oocytes: CLBR = 60.60%
- >20 oocytes: CLBR = 64.59%
Each increase in oocyte count significantly enhanced CLBR (P < 0.05), emphasizing the role of ovarian reserve and stimulation efficacy.
Age Stratification
Age profoundly affected outcomes:
- Women <35 years: CLBR = 56.37% (7,306/12,961). Tubal factor infertility had the highest CLBR (60.26%), while “other female factors” had the lowest (39.16%).
- Women ≥35 years: CLBR = 32.33% (1,622/5,017). Pelvic/tubal factors still dominated (36.84%), but ovulatory dysfunction yielded the lowest CLBR (23.14%).
Protocol efficiency varied by age:
- <35 years: Long protocol CLBR = 58.56%; antagonist protocol = 47.82%.
- ≥35 years: Long protocol CLBR = 37.75%; short protocol = 20.45%.
Multivariable Regression Analysis
Logistic regression identified seven independent prognostic factors (Table 2):
- Female Age: Odds ratio (OR) = 0.947 (P < 0.001).
- BMI: OR = 0.983 (P = 0.001).
- Infertility Duration: OR = 0.990 (P = 0.048).
- COH Protocol: Long protocol outperformed others (P < 0.001).
- Gonadotropin Dosage: Higher doses reduced success (OR = 1.000, P < 0.001).
- Oocyte Count: Retrieving >15 oocytes increased odds (OR = 1.410, P < 0.001).
- Transferrable Embryos: Each additional embryo improved odds (OR = 1.151, P < 0.001).
Age-Specific Variations
For women <35 years, BMI (OR = 0.983) and infertility type influenced outcomes, while male age (OR = 0.979) and protocol choice were critical for those ≥35 years (Tables 3–4). The antagonist protocol underperformed in older women (OR = 0.698), highlighting age-dependent protocol optimization needs.
Discussion
Clinical Implications of CLBR
CLBR’s value lies in aggregating outcomes across fresh and FET cycles, providing a comprehensive success metric. This study underscores that CLBR is influenced by modifiable (e.g., COH protocol, gonadotropin use) and non-modifiable factors (e.g., age, ovarian reserve).
Oocyte Retrieval and Embryo Quality
The direct correlation between oocyte yield and CLBR aligns with prior research, where optimal retrieval (15–20 oocytes) maximized success while balancing ovarian hyperstimulation syndrome (OHSS) risks. Younger women with higher reserves benefit from aggressive stimulation, whereas older women require careful protocol selection to optimize limited oocytes.
Age as a Determinant
Age-related declines in oocyte quality and endometrial receptivity are well-documented. This study confirms that female age >35 reduces CLBR by nearly half, emphasizing the need for early ART intervention. Male age also marginally impacts outcomes, likely through sperm DNA integrity changes.
Protocol Optimization
Long protocols yielded higher CLBR across age groups, likely due to better synchronization of follicular development. Antagonist protocols, while reducing OHSS risks, showed lower efficacy, particularly in older women. Individualized COH protocols tailored to ovarian reserve and age are crucial.
Limitations and Future Directions
As a single-center retrospective study, generalizability may be limited. Prospective multicenter studies could validate these findings. Additionally, genetic and epigenetic factors affecting embryo quality were not explored but warrant future investigation.
Conclusion
This large-scale analysis identifies female age, BMI, infertility duration, COH protocol, oocyte yield, and transferrable embryos as pivotal factors affecting CLBR. For women <35, optimizing oocyte retrieval and selecting long protocols enhance success. Older women benefit from individualized protocols and managing expectations based on diminished ovarian reserve. CLBR serves as a robust metric for counseling and clinical strategy, promoting realistic patient expectations and informed decision-making.
doi:10.1097/CM9.0000000000001586
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