P–616 Novel approaches for preventing ovarian hyperstimulation syndrome in breast cancer patients
Authors: Tatiana N , Martirosyan Y , Dmitrieva I , Biryukova A , Parokonnaya A 
Published: August 2021

Abstract

Study question
In this study we tried to assess the effectiveness of the use of aromatase inhibitors (AI) for the rapid relief of symptoms of hyperstimulation in patients with breast cancer.

Summary answer
AI showed great efficiency for OHSS prevention and are particulary useful in fertility preservation, when supraphysiologic estradiol levels cause a negative impact and delay treatment.

What is known already
To date the only unequivocally accepted method for fertility preservation is cryopreservation of embryos and unfertilized oocytes. However, controlled ovarian stimulation is associated with supraphysiological serum estradiol level. The majority of guidelines recommend to use aromatase inhibitors during ovarian stimulation (OS) in breast cancer patients with high estrogen receptor expression to protect them from the potential deleterious effects of elevated estrogen. Following oocyte retrieval the patients will be receiving chemotherapy, which is not desirable for hyperstimulated ovaries. The prolonged use of AI seems to be an interesting approach in such cases.

Study design, size, duration
This research was conducted at the V.I. Kulakov NMRC for OG&P to demonstrate management tactics for OHSS prevention after OS in patients with breast cancer. It included 21 patients seeking cryopreservation of oocytes and embryos. The main outcomes included the results of dynamic steroidogeneses assessment, the size of the ovaries, main features of oogenesis and the onset of the menstrual blleding. All patients signed an informed consent form approved by Ethics Committee.

Participants/materials, setting, methods
The mean age of the participants was 26.7. The patients presented prior to gonadotoxic treatment for luminal A or B breast cancer, were randomly divided into two groups of 11 and 10 people and underwent conventional OS with letrozol (2.5 mg/day). Starting from the day of oocyte retrieval the AI dosage iIn the 1st group was increased to 0.75 mg/day; the 2nd group received GnRH antagonist (0.5 mg/day) instead of AI for 5 consecutive days.

Main results and the role of chance
The mean age, BMI and AMH were not different among groups. There was no statistically significant difference in the duration of stimulation and starting and total doses of gonadotropins. The mean number of retrieved oocytes was 15.3 for the 1st group and 16.1 for the 2nd group (p = 0.834). There was no significant difference in a number of mature oocytes between the groups (66.1% vs. 72.4% in the 2nd group, p = 0.059) or in how many of them formed into 2pn embryos after fertilization (80% vs. 73.9% in the 2nd group, p = 0.616). Steroid hormone levels were analyzed during OS and on days 2 and 5 after oocyte retrieval. The rapid decline in serum estradiol and progesterone levels manifested with ovary size reduction and the onset of menstrual bleeding, which were achieved on 3rd to 5th day of AI administration in the 1st group and on 5th to 7th day of GnRH antagonist administration in the 2nd group.

Limitations, reasons for caution
Further research is required to compare the mechanisms of luteolysis induced by aromatase inhibitors and GnRH antagonists to natural luteal regression.
Wider implications of the findings: Our data has demonstrated a greater efficiency of AI compared to GnRH antagonists in reducing the risk of OHSS. These findings could be useful for future research and clinical use in patients without cancer but with a high risk of developing OHSS combined with segmentation of IVF treatment.

Trial registration number
none