What is super ovarian stimulation?

Super Ovarian Stimulation: A Medical Overview

Super ovarian stimulation, more commonly known as controlled ovarian hyperstimulation (COH), is a medical procedure that involves the administration of medications to stimulate the development of multiple ovarian follicles simultaneously, rather than the single follicle that typically develops during a natural menstrual cycle.

Definition and Purpose

Controlled ovarian hyperstimulation is a fundamental component of assisted reproductive technologies (ART) that aims to:

• Induce the growth of multiple follicles simultaneously
• Increase the number of oocytes available for collection
• Enhance the chances of successful fertilization and pregnancy
• Provide multiple embryos for selection and/or cryopreservation

Medications Used for Ovarian Stimulation

Several medications are employed in ovarian stimulation protocols:

1. Gonadotropins:

   • Follicle Stimulating Hormone (FSH)
   • Human Menopausal Gonadotropin (hMG)
   • Recombinant FSH (rFSH)

2. GnRH Agonists and Antagonists:

   • Used to prevent premature ovulation by controlling the release of natural hormones

3. Ovulation Triggers:

   • Human Chorionic Gonadotropin (hCG)
   • GnRH agonists

4. Adjunctive Medications:

   • Aromatase inhibitors (letrozole) - particularly for patients with estrogen-sensitive cancers 1
   • Clomiphene citrate
   • Tamoxifen 1

Stimulation Protocols

Different protocols have been developed for various patient populations:

• Long Protocol: GnRH agonist started in the luteal phase of the previous cycle
• Short Protocol: GnRH agonist started at the beginning of the stimulation cycle
• Antagonist Protocol: GnRH antagonist added after stimulation has begun
• Random-start Protocol: Stimulation initiated regardless of menstrual cycle phase 2
• Double Stimulation: Stimulation performed twice in the same cycle for poor responders 2

Clinical Applications

1. In Vitro Fertilization (IVF):

   • Standard approach for embryo creation
   • Requires 10-14 days of ovarian stimulation 1

2. Fertility Preservation:

   • For cancer patients prior to gonadotoxic treatments 1
   • Can be combined with oocyte or embryo cryopreservation

3. Treatment of Infertility:

   • For anovulatory patients to induce ovulation
   • For ovulatory patients to increase chances of conception

Procedure and Monitoring

The process typically involves:

1. Baseline evaluation of ovarian reserve
2. Administration of stimulation medications for 10-14 days
3. Regular monitoring with:
   • Transvaginal ultrasounds to measure follicular growth
   • Blood tests to assess hormone levels
4. Trigger injection when follicles reach appropriate size
5. Oocyte retrieval 34-36 hours after trigger
   • Performed under anesthesia via transvaginal ultrasound-guided aspiration 3

Risks and Complications

Key risks include:

• Ovarian Hyperstimulation Syndrome (OHSS):

  • Potentially serious complication characterized by ovarian enlargement and fluid shifts
  • More common with hCG triggers and in young patients with high antral follicle counts

• Multiple Pregnancy:

  • Higher risk when multiple embryos are transferred
  • Can be mitigated through single embryo transfer policies

• Procedural Risks:

  • Bleeding or infection from oocyte retrieval (rare in patients with normal hematopoiesis) 1

Special Considerations

For Cancer Patients

• Stimulation can be started at any time of the menstrual cycle ("random start stimulation") 1
• For hormone-sensitive cancers (e.g., breast cancer), protocols using letrozole or tamoxifen can reduce estrogen exposure 1
• No evidence that ovarian stimulation increases cancer recurrence risk 1

For Poor Responders

• Combined protocols using different types of FSH may improve outcomes 4
• Double stimulation within the same cycle may optimize results 2

Efficacy

The success of ovarian stimulation is influenced by:

• Patient age: Higher oocyte yield in younger patients (15.4 ± 8.8 in women <26 years vs. 9.9 ± 8.0 in women 36-40 years) 1
• Ovarian reserve
• Stimulation protocol
• Underlying fertility issues

Live birth rates after oocyte cryopreservation are approximately 61.9% if 12 oocytes are preserved in women ≤35 years and 43.4% if 10 oocytes are preserved in women >35 years 1.

Conclusion

Controlled ovarian hyperstimulation is a cornerstone of modern fertility treatments, enabling the collection of multiple oocytes to maximize the chances of successful pregnancy. The protocol should be tailored based on the patient's age, ovarian reserve, and specific clinical circumstances, with special considerations for patients with cancer or other medical conditions.