Is modified natural cycle IVF justified in patients with “genuine” poor ovarian response?

Natural cycle IVF has been proposed as an option for poor responder patients. In this approach, conventional stimulation with fertility drugs is not used. The patient is monitored for development of a dominant follicle that is then punctured (just prior to ovulation) and the eggs retrieved. Only one egg is retrieved but there are some data suggesting that the QUALITY of this egg is superior and hence can result in a pregnancy. In order to prevent premature ovulation a modification of the protocol was proposed. In modified natural cycle (MNC)-IVF, a GnRH antagonist is added when the follicle measures 13 mm in diameter and hMG (a fertility drug) is co-administered. This approach works well in “normal” responder patients with pregnancy rates approaching 10% per attempt. The question is whether this approach works in patients with POR>

Poor Responder Patients Remain A Major Challenge

Poor responder patients remain a major challenge even today. Various strategies have been proposed to improve outcome in this difficult group of patients. These include use of GnRH antagonist, reducing or stopping the dose of GnRH agonist (GnRH-a), the ultrashort, short, and microdose GnRH-a “flare” protocols, a combination of the two, use of letrozole, or the modified natural IVF cycle. There is no consensus as to which is the “best” approach for poor responder patients.

A major obstacle in comparing treatment protocols was the wide variation in the definition of a “poor” responder. A recent advance was a consensus definition that has been discussed in a previous blog. According to the Bologna criteria, the minimal criteria needed to define “poor ovarian response” (POR) are the presence of at least two of the following three features: [1] advanced maternal age (greater than 40 years) or any other risk factor for POR; [2] a previous POR (3 or fewer oocytes with a conventional stimulation protocol); and [3] an abnormal ovarian reserve test.

In a recent publication Kedem et al. (from the Chaim Sheba Medical Medical Center in Israel) have presented their experience with modified natural cycle (MNC) IVF in 111 patients with POR (that met the Bologna criteria) over a 12 year period (Fertility Sterility 2014; in press). The MNC-IVF protocol consisted of women who underwent natural cycles with GnRH antagonist supplementation. The GnRH antagonist treatment (0.25 mg/day; Cetrorelix, Cetrotide, Serono International SR) was started when a follicle of 13 mm was present. Two to three ampules of hMG (Menogon) were co-administered daily during the GnRH antagonist treatment. Egg retrieval, embryology and progesterone use was as per routine. The results were interesting.

The MNC-IVF cycle was compared with the previous conventional IVF cycle. In the MNC-IVF cycle, less medication was used. Also the peak estradiol level, number of eggs retrieved, and number of embryos transferred were lower in the MNC-IVF cycle. In the MNC-IVF group; 43 cycles had no eggs retrieved and 52 cycles did not have an embryo transfer! There was ONE pregnancy (out of 111 cycles!) that resulted in a live birth.

They also analyzed data from 58 patients that had one egg retrieved during a previous conventional IVF cycle. There were NO pregnancies in this group of patients.

Of interest is the fact that when patients with “genuine” POR subsequently had another conventional IVF cycle; the clinical pregnancy and live birth rates were 4.9% and 4% respectively.

The authors conclude that the potential of MNC-IVF is limited for genuine poor ovarian responders. According to the data presented, MNC-IVF should not be offered to this group of poor responders and the option of a conventional COH-IVF, egg donation, or adoption should be seriously considered at this point. At InVia Fertility Specialists, we do not offer MNC-IVF to patients with POR.