Random-Start Controlled Ovarian Stimulation Effective in Fertility Preservation in Cancer Patients

Introduction

Fertility preservation by controlled ovarian stimulation (COS) for mature oocyte of embryo cryopreservation is usually done in cancer patients. Conventionally, COS is initiated at the start of follicular phase which may take 2-6 weeks. In case of down-regulated cycles, ovarian simulation can be started only after the menses begin. Hence, there is a possibility of significant delay of cancer treatment leading to increased psychologic stress for the patient and oncologist. Protocols with alternative timing to initiate COS have been proposed. However, there are no studies which have compared the COS outcomes to conventional stimulation.

Aim

To compare the outcomes of random-start COS irrespective of the menstrual phase to conventional early follicular phase-start COS for fertility preservation in cancer patients.

Method

Study Design

• Retrospective cohort study

Treatment Strategy

• Women with recent diagnosis of cancer, who were in preparation for chemotherapy/radiotherapy or bilateral oophorectomy were included
• A total of 128 cancer patients underwent IVF cycles using GnRH antagonist for pituitary suppression.
• Initial dosage of gonadotropins (Follitropin and/or Menotropin) was selected based on the patient's age, BMI, and an assessment of ovarian reserve.
• Conventional-start COS was done in 93 patients (109 cycles) and random-start COS in 35 patients (35 cycles).
• Letrozole 2.5 or 5 mg/d was started with the ovarian stimulation and continued until hCG or GnRH agonist trigger if the patient had estrogen-sensitive malignancy.
• Oocyte and embryo cryopreservation were done in 45% and 52.3% in conventional-start cycles and in 62.9% and 37.1% in random-start cycles, respectively.

Primary End Point

• The number of mature (MII) oocytes retrieved

Secondary End Points

• Pattern of follicular development
• Total number of oocytes retrieved
• Oocyte maturity rate (MII oocytes/total oocytes)
• Oocyte yield (total number of oocytes retrieved/AFC)
• Mature oocyte yield (number of mature oocytes retrieved/AFC)
• Total dosage of gonadotropins needed
• Average daily dosage of gonadotropins
• Number of days needed for ovarian stimulation
• Fertilization rate

Results

• The baseline characteristics such as age, body mass index and pregnancy-history were similar between both the groups
• Breast cancer was diagnosed in 77.1% and 70.8% in the random-start and conventional-start cycles respectively
• There were no significant differences in the number of total and mature oocytes retrieved, oocyte maturity rate, mature oocyte yield, and fertilization rates in both groups.
• The outcomes are shown in table 1.

• No superiority was observed when COS started in the late follicular (n = 13) was compared to that in the luteal phase (n = 22).
• COS outcomes or oocyte maturity and competence were not adversely affected by the addition of letrozole, in the case of estrogen-sensitive cancers, in either random- or conventional-start protocols.

Conclusion

• Random-start controlled ovarian stimulation (COS) was as effective as conventional-start COS in fertility preservation in cancer patients
• Random-start COS significantly decreased the total time for an IVF cycle without affecting the oocyte yield, maturity or competence
• This protocol would minimize delays and allow more patients to undergo fertility preservation and still proceed with cancer treatment within 2–3 weeks.

Fertil Steril 2013;100(6):1673-80.