Delayed IVF for PCOS patients

Immature eggs retrieved during an IVF cycle normally don’t make healthy embryos on fertilization but if they are allowed to mature in the laboratory for an extra day, they may turn into healthy, mature eggs that are capable of fertilizing well. This extension of the development potential of immature eggs is called delayed IVF.

Using this method, the slower-developing eggs are allowed to mature under controlled conditions in a laboratory so that they can become viable for use in IVF treatment.

Delayed IVF for PCOS patients

This additional step is a cost-effective way to help improve the chances of fertilization in an IVF cycle that would otherwise be abandoned due to inadequate quality of eggs.

Egg retrieval in IVF

When a woman enters her reproductive years, she starts to ovulate once every month. In every cycle, a new set of primary oocytes begin to mature (in a process called – oocyte maturation) and a developed egg is released from one of her ovaries. The matured egg or ovum then travels to the fallopian tube where it waits for fertilization with the sperm.  

During the egg retrieval stage of a traditional IVF, the COCs (or ‘cumulus oocyte complexes’ that contain both the egg and its surrounding fluid) are pulled off using a microneedle and processed for fertilization in the lab. Follicles measuring 15 mm to 18 mm are ideally required for successful egg retrieval.

Egg retrieval in PCOS patients

In the absence of mature eggs in the COC, the IVF cycle may be canceled, but if your clinic is equipped to deploy in-vitro maturation of eggs, you could simply adapt to delayed IVF.

Benefits of delayed IVF

In delayed IVF, any immature oocyte is matured in the lab using hormonal drugs, oocyte growth factors (such as the protein dimer – ‘cumulin’), while it is allowed to develop under controlled conditions. The fully matured oocytes are then used exactly as they would have been in a conventional IVF cycle.

The procedure allows for maturation of immature oocytes, improves chances of fertilization, generates additional embryos, improves blastocyst production rate, and thus, increases your chances of conceiving—all before your doctor decides to cancel the cycle. 

With delayed IVF there is no delay in transferring the embryo—you can opt for fresh or frozen embryo transfer.

The original process of oocyte in vitro maturation (IVM) or delayed IVF has been available since the 1990s, but not all clinics offer the treatment as it is technically quite challenging.

Can eggs fertilize after 24 hours of OPU?

In some cases, it may be possible for eggs to fertilize after 24 hours of the ovum pick-up (OPU). As the immature eggs are kept in the laboratory and left to mature in incubators under optimal conditions for about 24 hours, if any of them mature adequately, the sperm can be introduced into the egg, preferably through ICSI.

The fertilized egg is then cultured for 5 days to obtain a blastocyst (in some cases it may be considered to grow the blastocyst up to day 7). Once they are ready, the most viable embryos are implanted in the uterus.

Fertilization of immature eggs

Can eggs fertilize after 48 hours of OPU?

There isn’t enough evidence that shows eggs can develop through IVM after 48 hours of retrieval.

Who should consider delayed IVF?

Delayed IVF or oocyte maturation or IVM is offered to patients who have PCOS or are at risk of developing ovarian hyperstimulation syndrome (OHSS) with gonadotropin stimulation (1).

It may also be helpful in women with a poor ovarian reserve, an abundance of immature eggs, facing multiple cycle cancellations, or patients with low progesterone levels.

The evidence for the success of this procedure can also be found in a study where immature oocytes in low responders (those having less than 7 mature oocytes) from different age groups were cultured for an additional 18 to 24 hours in 434 IVF cycles (2). It was found that delayed-ICSI generates additional blastocysts for low responders.

Thus, the extensive procedure can be used to optimize the IVF cycle and clinical outcomes. 

A woman opting for delayed IVF should preferably have healthy fallopian tubes, good endometrium receptivity, and a male partner with a healthy semen analysis.

Expert opinion on delayed IVF

Dr. Colin Lee, a renowned fertility specialist in Malaysia reveals that successful pregnancies had resulted from transferring delayed-ICSI embryos from eggs that would have been discarded otherwise.

As per Dr. Lee, it could be a good option for patients who are unlikely to have a good number of normally fertilized eggs in the traditional approach. Such patients should have their immature eggs cultured for another day with delayed-ICSI to generate more utilizable blastocysts.

Are normal results achieved with delayed IVF?

After carrying out pre-implantation genetic testing (PGT) on the embryos to identify any abnormalities, Dr. Lee’s clinic found that “blastocysts cultured this way can be chromosomally normal, and therefore safe for embryo transfer.”

Success story with delayed IVF

Although delayed IVF has been practiced for decades and is no longer considered experimental, the uptake of the technique in clinical practices is quite limited. One such success story is of Peggy and Tim at our partner fertility clinic in Malaysia.

Knowing that delayed IVF might offer them their last chance to become parents, Tim and Peggy sought treatment under Dr. Lee’s guidance. During the treatment, Peggy’s eggs were obtained and kept for maturation in the lab for 18-24 hours. This was followed by injection of Tim’s sperm directly into the egg and the resultant embryos were then cultured for up to 7 days. In the end, the most viable embryos from the lot were implanted in Peggy’s uterus.

Peggy conceived successfully and gave birth to a healthy baby boy.

How long after ICSI does fertilization occur?

Once the mature egg and sperm are combined, it takes about 18 hours to establish whether fertilization has occurred. It may take another 2 to 4 days to determine whether an embryo is developing optimally.

However, do note that fertilization fails in 1-3% of cycles even after ICSI. In most cases, it is due to the low number of mature oocytes, failure of oocyte activation, or non-availability of appropriate spermatozoa for injection (3).

In such cases, delayed IVF or IVM, IVF with donor sperm or other fertility treatments may be recommended.

Conclusion

Delayed IVF is a low-intervention, mild approach to ART, which is also cost-effective as it reduces the need of undergoing multiple IVF cycles.

In the future, it may become a routine procedure in fertility clinics to help improve the IVF outcomes of selected patients, especially those who are poor responders. However, if it still does not work for you due to egg quality problems, you may have to consider IVF with donor eggs.

If you have more questions on what is delayed IVF or what is in vitro maturation, reach out to us using the contact form.

Resources:

  1. Kyung Sil Lim, Soo Jin Chae, Chang Woo Choo, Yeon Hee Ku, Hye Jun Lee, Chang Young Hur, Jin Ho Lim, and Won Don Lee. In vitro maturation: Clinical applications. Clin Exp Reprod Med. 2013 Dec; 40(4): 143–147. Published online 2013 Dec 31. [doi: 10.5653/cerm.2013.40.4.143]
  2. Z Q Tee, J P Sam, A Y X Lim, C S S Lee, P–220 Delayed-ICSI on day1-matured oocytes in low responders of different age groups. Human Reproduction, Volume 36, Issue Supplement 1, July 2021. [https://doi.org/10.1093/humrep/deab130.219]
  3. Murid Javed, Navid Esfandiari, Robert F Casper, Failed fertilization after clinical intracytoplasmic sperm injection, Reprod Biomed Online. 2010 Jan;20(1):56-67. DOI: 10.1016/j.rbmo.2009.10.010.

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