Is a human chorionic gonadotropin (hCG) trigger shot necessary during natural cycles using estradiol (E2)?

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Last updated: March 9, 2025View editorial policy

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From the Guidelines

The HCG trigger shot is not necessary during natural cycles using estradiol (E2) as the body typically produces its own luteinizing hormone (LH) surge to trigger ovulation. In a natural cycle supplemented with estradiol, estradiol is primarily used to support endometrial development and improve the uterine lining for potential implantation, rather than to control ovulation timing 1. According to the study by Cantineau et al. (2014), the timing of insemination is one of the most important factors influencing the outcome of IUI, and in natural cycles, LH testing is the most applied method for timing 1.

The study also mentions that if a HCG injection is used, single IUI can be performed any time between 24 and 40 h after HCG injection without compromising pregnancy rates 1. However, in natural cycles, IUI should be performed 1 day after LH rise, which suggests that the natural LH surge is sufficient for timing ovulation 1.

Some key points to consider when deciding whether to use an HCG trigger shot include:

  • The specific treatment goals and whether spontaneous ovulation detection through ultrasound monitoring and LH testing is sufficient
  • The need for precise timing of ovulation for procedures like intrauterine insemination or egg retrieval
  • The potential for a less predictable or inadequate natural LH surge in some patients, which may require supplementation with HCG 1.

Overall, the decision to use an HCG trigger shot during natural cycles using estradiol should be based on individual patient needs and treatment goals, with consideration of the potential benefits and risks of supplementation.

From the Research

Human Chorionic Gonadotropin (hCG) Trigger Shot in Natural Cycles Using Estradiol (E2)

  • The necessity of a human chorionic gonadotropin (hCG) trigger shot during natural cycles using estradiol (E2) is a topic of debate in the field of reproductive medicine.
  • A study published in 2011 2 found that triggering ovulation by hCG can significantly reduce the number of visits necessary for cycle monitoring without an adverse effect on cycle outcome in patients undergoing natural-cycle frozen-thawed embryo transfer (FET).
  • Another study from 2017 3 compared the use of hCG triggering with urinary LH monitoring for timing therapeutic donor inseminations in natural cycles and found that cumulative live birth rates were comparable between the two groups.
  • A 2011 study 4 compared letrozole-stimulated cycles to natural cycles in patients undergoing intrauterine insemination (IUI) and found that letrozole treatment resulted in some minor changes in follicular, hormonal, and endometrial dynamics compared to natural cycles.
  • A retrospective study from 2018 5 compared FET outcomes in natural cycles according to ovulation induction (spontaneous versus recombinant human chorionic gonadotrophin (r-hCG) triggering) and found no significant difference in implantation rate, clinical pregnancy rate, and live birth rate between the two groups.
  • A 2022 study 6 analyzed the optimal timing of ovulation triggering in natural cycles based on follicle size and oestradiol concentration and found that the number of retrieved oocytes was associated with E2 concentration, and maturity of oocytes was associated with both E2 concentration and follicle size.

Key Findings

  • The use of hCG triggering in natural cycles may reduce the number of monitoring visits required without affecting cycle outcome 2.
  • Urinary LH monitoring may be as effective as ultrasound monitoring and ovulation trigger with HCG in therapeutic donor inseminations performed in natural cycles 3.
  • Letrozole treatment can result in minor changes in follicular, hormonal, and endometrial dynamics compared to natural cycles 4.
  • There may be no significant difference in FET outcomes between spontaneous ovulation and r-hCG triggering in natural cycles 5.
  • The optimal timing of ovulation triggering in natural cycles may depend on follicle size and oestradiol concentration 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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