Comparing IVF protocols and genetic testing outcomes

This study looked at two protocols for in vitro fertilization (IVF) using different timing of medications to suppress the body’s own hormones. It found that patients using a long-acting protocol had fewer embryos with unusual chromosomes (genetic material).

Women are born with most of their oocytes (eggs) already formed. However, the oocytes are in a suspended state and their chromosomes are still doubled. During each menstrual cycle several oocytes develop until one is ready. At this point, the pituitary gland in the brain releases luteinizing hormone (LH). The LH causes ovulation. The LH also causes the chromosomes to resume dividing, which will make them ready for fertilization. However, sometimes this process occurs incorrectly, and the oocyte is left with the wrong number of chromosomes or misplaced chromosome pieces.

The infertility treatment IVF involves using medications to stimulate the ovaries to produce multiple oocytes (eggs). It is important to prevent early ovulation before the oocytes can be collected. This requires preventing the body’s own gonadotropin-releasing hormone (GnRH), which is the hormone that stimulates LH.

One method to do this is with GnRH agonist, which mimics the body’s own GnRH. Exposed to constant GnRH agonist, after a while the pituitary stops responding to it. Traditionally, GnRH agonist is started during the second half of the cycle before IVF. This method is known as the mid-luteal short-acting long protocol (MLSL). However, an alternate method is to start the GnRH agonist even earlier, before ovulation of the cycle before IVF. This is the early follicular long-acting long protocol (EFLL). Some studies have found that EFLL has higher pregnancy rates than MLSL. It is not clear whether there is a difference in how many oocytes have the correct number of chromosomes.

This study included 310 IVF cycles. 62 cycles used EFLL and 248 used MLSL. 1,541 resulting embryos underwent preimplantation genetic testing (PGT), which checks for abnormal chromosomes.

PGT for aneuploidies (PGT-A) tests whether there is an extra or missing chromosome. 125 cycles were tested with PGT-A. 44.6% of EFLL embryos had normal chromosomes, compared to 36.9% of MLSL embryos. 

PGT for structural rearrangements (PGT-SR) tests whether a piece of a chromosome is in the wrong location. 185 cycles were tested with PGT-SR. There were significantly more embryos with normal chromosomes per cycle when using EFLL (1.76 vs 1.21).

This study found that EFLL may lead to more embryos with normal chromosomes than MLSL in couples undergoing IVF.

This study used medical records. Patients who used EFLL may have had differences from those who used MLSL. Studies are needed which randomly assign patients to a protocol. Also, it is not clear how these results compare to GnRH antagonist, which is another method to suppress GnRH.