Fertility Studies

Improving Implantation of Slower Growing Embryos

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When using slower developing embryos, implantation timing is key to getting pregnant, according to research from Reproductive Medicine Associates of NY.

The reduced implantation rate of slower developing blastocysts (day 5 embryos) is primarily a result of asynchronous endometrial development, not the quality of the embryo, according to data presented by Reproductive Medicine Associates of NY at the American Society for Reproductive Medicine 2015 Annual Meeting.

Implantation rates improve if the slower developing embryos are frozen, thawed, then transferred to a well-prepared, properly synchronized uterine environment.

“The implantation of the embryo into the uterus is an orchestrated event. There is a very narrow window of time where the lining of the uterus will permit an embryo to attach and grow,” says Dr. Tanmoy Mukherjee, co-director of RMA of NY. “It can be the healthiest embryo in the world, but if it isn’t implanted at the right time, you’re not going to get pregnant.”

The retrospective study included patients who underwent fresh, single embryo transfer with IVF from 2010-2015. Researchers compared implantation rates of slow versus normal developing embryos under a synchronous and asynchronous endometrium (uterine lining).

“What we mean by synchrony is the embryo enters the uterine cavity at the right time for implantation to be possible,” Mukherjee explains. “On day 14, out of a 28-day cycle, you ovulate,” Mukherjee explains.

Conception occurs in the next 2 to 3 days. Then, 2 to 3 days later, the embryo enters the uterus as a blastocyst, not a day 3 embryo, to attach and grow. This is when the timing issue comes in— a bump in progesterone is the trigger that tells the uterine lining that there’s an embryo on the way.

This premature progesterone elevation signals the onset of the window of implantation. That implantation rate may be decreased if the embryo is not advanced enough to implant during the narrow window of time.

“Age for age, no matter how good your embryo look, if progesterone is not secreted in coordination with embryo development the transfer will occur outside of the optimal window of implantation and be less successful,” Mukherjee says.

Freezing embryos is the best way to control the window of implantation because it allows the doctor to use the next month to properly prepare the endometrium, Mukherjee notes.

“I will absolutely be able to control the exposure to progesterone in a very timed sequence, so I know that I’m hitting the window of implantation ideally. It improves outcomes; we’re very enthusiastic about it,” he says.

Now that researchers have good data regarding the effect of progesterone on the window of implantation and the benefit of controlling the progesterone environment precisely with medicated endometrial preparation, the next question they sought to answer is: Why do embryos that are slow but chromosomally normal fail to implant?

In some patients who show delayed embryo development, embryonic development may not be complete until after the window of implantation has closed. In these cases, freezing and transferring in a subsequent controlled cycle appears to be beneficial.

Regardless of premature endometrial receptivity or delayed embryonic maturity, freezing all cycles with preimplantation genetic testing for aneuploidies (PGT-A) and eventual transfer into a properly prepared endometrium confers a better outcome, in the research team’s clinical experience.

Dr. Tanmoy Mukherjee, a board-certified Gynecologist and Reproductive Endocrinologist, is Associate Director of the Mount Sinai Division of Reproductive Endocrinology and co-director of Reproductive Medicine Associates of New York. He completed his residency at the Albert Einstein College of Medicine where he received the Leo M. Davidoff Society Award as well as the Schulman Award, and completed his fellowship at Mount Sinai Hospital. The author of numerous journal articles and textbook chapters, Dr. Mukherjee is also the recipient of the prestigious Society of Reproductive Surgeons Award for his extensive research in ovum donation and medical therapy for the treatment of infertility. 

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