A new trial to reduce the failure of IVF/ICS protocols in severe endometriosis

A shortened protocol paper to shorten induction prior to IVF/ICSI among endometriosis patients

Key Points

Highlights:

• The women with endometriosis often have lower pregnancy rates after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and the administration of GnRH agonist (GnRH-a) prior to the procedure helps to increase clinical pregnancy rates. This trial aims to find a safer and more effective ovulation induction regimen specifically for patients with endometriosis. 

Background:

• In a typical ultra-long-acting regimen, 2–3 doses of long-acting GnRH-a is administered prior to ovulation induction to create a low estrogen status, for driving endometriosis foci undergoing atrophy, then ovulation induction is executed by gonadotropin. In this regimen, the treatment cycle is long, there are more side effects of low estrogen and the use of gonadotropins is high. 
• To ensure a good pregnancy rate while reducing the above negative effects during the treatment, whether a briefer treatment interval is efficacious has been offered for comparison.

Importance:

• If using one dose of long-acting GnRH-a is equivalent to two doses of GnRH-a for IVF-assisted pregnancy for patients with endometriosis, the treatment cycle will be shortened and the total dose of gonadotropin used will be reduced.

What's done here:

• The authors planned a multi-center, randomized controlled clinical trial of the application of a shortened protocol of long-acting Triptorelin down-regulated prior to IVF/ICS cycles in three reproductive centers.
• The primary outcome is the clinical pregnancy rate.
• Additional outcomes are gonadotrophin duration, the necessary total dose of follicle-stimulating hormone, the number of oocytes retrieved and the embryos available for transfer, the implantation/abortion rate, live birth rate, and the incidence of moderate-to-severe ovarian hyperstimulation.
• The sample size is estimated to be 421 participants for each arm.
• All women should have confirmed endometriosis by laparotomy or laparoscopic surgery and necessitate receiving assisted pregnancy treatment.
• The scheme of shortened GnRHa protocol is detailed in the paper, the first visit being day 2 of the cycle and the fifth visit being embryo transfer. A total of nine visits are planned.

Lay Summary

Kong et al., from the first affiliated hospital of Zhengzhou University, China, recently published this single-blinded, a multicentered and randomized controlled study in the Journal of Reproductive Health, with the aim to find a safer and more effective ovulation induction regimen for patients with endometriosis. 

In the long-term GnRH agonist (GnRH-a) regimen of patients with endometriosis, to create a low estrogen status which serves to depress the ectopic endometrial tissues, 2 to 3 doses of long-acting Triptorelin is given prior to ovulation induction, and, after that, gonadotropin is used for induction.

Unlike this method, authors aimed to assess using one dose of long-acting Triptorelin to give better results to achieve more fresh embryo transfers, to increase clinical pregnancies and less treatment cost with shorter regimen time. 

To examine the difference between long and short GnRH-a protocols the authors offered a protocol to compare the pregnancy rates, E2 and P levels on the day GnRH-a administration, number of oocysts retrieved, Gn duration and dosage, metaphase II ratio during ICSI injection, available embryos to transfer, fresh cycle to transfer cycle ratio, the incidence of OHSS and rates of implantation, early miscarriage, ectopic pregnancy, ongoing pregnancy, multiple pregnancy, and live birth. Several statistical significance tests will be used to determine the differences between control and study groups at the end of the study.

In conclusion, to provide a safer and more effective ovulation induction and less discomfort for patients with endometriosis, authors give a try to create a shorter protocol and will share their results of 421 patients for each arm at the end of this study. The main benefits of the shorter protocol are shortened treatment cycle and less amount of Gn used in this course.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/30572916