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Oocyte Maturation for IVF

In Vitro Maturation (IVM) was developed as an alternative to traditional Oocyte Maturation for IVF due to the adverse outcomes of ovarian hyperstimulation syndrome and the costs

Associated with the administration of FSH. The treatment also has the potential to overcome other causes of infertility such as male factor, and poor response to stimulation, and also has profound benefits for women who have an estrogen-sensitive tumor or with a prothrombotic medical condition and are undergoing oocyte or embryo cryopreservation.

IVM consists of collecting immature (ie. Geminal Vesicle or GV) oocytes and applying FSH and HCG in the culture media. 

In vitro maturation of immature oocytes from an unstimulated cycle is an emerging technology. One of the safest ways to prevent OHSS is to not stimulate the ovaries. During an in vitro maturation of oocytes cycle, the immature eggs are retrieved from ovaries that are barely stimulated or completely unstimulated.  The eggs are maturated in defined culture media for 24 to 48 hours and fertilized through IVF or ICSI. IVM is an experimental technique that consists of the in vitro conversion of oocytes at the GV stage to oocytes at the metaphase II stage.

This technology must include nuclear and cytoplasmic maturation of the oocyte and give rise to embryos that have a developmental potential that is similar to embryos obtained from standard IVF or from spontaneously in vivo matured oocytes. A few IVM practitioners advocated for “rescue IVM” in IVF conventional settings to prevent severe OHSS. “Rescue IVM” is when the physician has come to the conclusion that a safe conventional IVF cycle cannot be done so they change the treatment direction to an IVM protocol to cycle instead. If the aspiration happens prior to the follicle selection, then OHSS risk can be eliminated. 

Though IVM shows promising results, it is not mainstream for fertility treatment. Mainly because there are difficulties retrieving eggs from immature ovaries that are not stimulated, and a lower chance of live births compared to conventional IVF, and there is an increased rate of abnormalities in meiotic spindles and chromosomes from immature eggs.

Are you a candidate for IVM?

According to ASRM In vitro maturation: a committee opinion, candidates for IVM include:

• Candidates for IVM may include women at risk for OHSS, including women with PCOS or PCO-like ovaries.
• Efficacy of IVM in the context of estrogen-sensitive cancers, or in women with limited time for initiating fertility preservation before undergoing potentially gonadotoxic cancer treatments, is still not clear.
• IVM provides an alternate treatment protocol for these groups of women, with reduced patient burden due to shorter stimulation cycles, fewer injections, and associated reduced drug and monitoring costs.
• IVM should be offered by those with expertise gained by specific training, and should always be accompanied by appropriate counseling about expected results and informed consent. This technology is no longer considered experimental.
• IVM is not applicable to every patient; only those with a high AFC are good candidates.
• Patients should be made aware that blastocyst conversion is lower and that implantation and pregnancy rates may be reduced compared with conventional IVF. 
• Large trials comparing clinical outcomes of promising newer methods of IVM versus standard IVF, as well as long-term follow-up studies of neonatal health and developmental outcomes of offspring, are necessary. 

Is IVM Useful to Reduce Early Pregnancy Loss in PCOS Patients?

Early pregnancy loss in patients with polycystic ovary syndrome after IVM versus standard ovarian stimulation for IVF/ICSI was investigated by Mackens et al., (Human Reproduction, 2020). They found:

• Pregnancy achieved following IVM seems to be at greater risk for early pregnancy loss (EPL) when compared with a pregnancy achieved following conventional ovarian stimulation (OS), but only when a fresh embryo transfer is performed.
• This observation leads us to suggest that IVM per se does not adversely influence embryo and fetal development in the first trimester and points towards inappropriate endometrial function in IVM cycles.
• Adopting a freeze-all strategy is currently the best approach for embryo transfer in the IVM program.
• A well-powered randomized controlled trial comparing the outcomes of a freeze-all approach after IVM versus standard OS in a well-defined phenotypic group of PCOS patients would be the next step to corroborate the current conclusion.