Natural Cycle IVF: An Overview

Minimal Simulation and Natural Cycle In Vitro Fertilization, Allahbadia, G and Nitzschke, M, 2015

Natural Cycle IVF: An Overview (Badiola, A and Suarez, N)

Dr Daiter’s summary of this chapter

In a review of available SART data from 2006-2007 only 13-16% of IVF clinics in the USA performed unstimulated IVF and only 1.5% of IVF cycles from those clinics offering unstimulated IVF were actually unstimulated.

In the general population, one report on 181 natural cycle IVF cases states that 48% of patients were over 35 years age, 82% of IVF starts resulted in egg retrievals, the pregnancy rate was 13% per cycle, and the cumulative pregnancy rate after 4 cycles was 46%.  In the patients under 35 years age, 54% of IVF starts reached embryo transfer and there was a pregnancy rate of 36% per embryo transfer (the implantation rate per embryo was actually higher compared to stimulated cycles in women 35-42 years old and there was no difference in implantation rates for women under 35 years old)

“Low responders” are thought to be particularly suited to natural cycle IVF since they don’t respond well to high doses of medications and many of these “challenging” cases are directed to donor egg IVF (despite their desire to try with their own eggs).  In one study of 500 natural cycles of IVF for 294 women considered “poor responders” results include successful egg retrieval in 78% of those reaching the egg retrieval procedure, suitable embryos for transfer after ICSI and cell culture occurred in 57% of those where eggs were successfully retrieved, and a clinical pregnancy rate of 10% per cycle or 17% per embryo transfer.  Despite different statistics for success at different centers, thought to be related to differing protocols and small numbers of cases, the decision to undergo this treatment for “low responders” remains a personal decision for the patients after proper counseling about the relative success rates and cost.

“Endometrial receptivity” (the implantation window is the few days a cycle during which the uterine endometrium is receptive to implantation by an embryo) has been characterized by the changes that occur in a few different markers (discovery of new markers is an active area of research, markers described to date include the formation of epithelial “pinopodes” and the expression of certain cell adhesion molecules and cytokines).  In studies, many reports are described as demonstrating a higher rate of embryo implantation in unstimulated versus stimulated IVF cycles in several different age groups of patients.  Also, implantation rates were higher in frozen embryo transfers using cryopreserved embryos versus fresh embryo transfers for stimulated cycles, in one study the clinical pregnancy rate was 84% per transfer in the cryopreserved group versus 55% per transfer in the fresh group.   The use of Letrozole (an aromatase inhibitor) from days 3-7 seems to be a good alternative when medications are needed to induce ovulation, since it reportedly has a stimulatory effect on the ovaries and a favorable effect on the endometrium.

“Complications” during natural cycle IVF include premature LH surge (although 71% of initiated cycles result in egg retrievals in one study), ovulation discovered at the time of retrieval, fertilization failure (can be largely overcome with ICSI), and embryo arrest.  The reported percentage of cycles resulting in an embryo transfer ranged from 54% (youngest patients) to 23% (patients over 42 years age).

“Premature ovulation” is a major cause of cycle cancelation.  Egg retrievals that are based on a patient’s natural LH surge require frequent serum monitoring and round the clock egg retrieval facilities (an ideal situation that is rarely realistic).  Another approach to egg retrieval involves triggering ovulation with hCG (allows greater control of scheduling the retrievals) and aspirating eggs with mulitple follicle flushes (can significantly increase the probability of retrieving an egg in natural cycle IVF, reportedly from about 30% to about 85%).  In the “modified natural cycle IVF” protocols, the natural LH surge is prevented using a GnRH antagonist medication close to expected ovulation (starting when lead follicle is 12-17 mm diameter) and the growth of the follicle is supported with the addition of gonadotropins.

The “oocyte recovery rate” in natural cycles was studied in 2000 in which 50 patients from age 22-38 years underwent 75 natural cycles of IVF and the egg recovery rate was 67% per cycle start and 82% per egg retrieval.  Of note, the egg retrieval with only one egg was considered much less painful than the retrieval of multiple eggs (during a conventional IVF protocol) and there is usually no need to take a cycle of rest between IVF cycles.

At the author’s IVF center, in 2011 there were 165 natural cycle IVF cases (27% of all cycles for that year at their center), 30% were for women less than 36 years age, including many women who for personal, moral, or medical reasons did not want to undergo conventional IVF, the outcome of 4 cycles of natural cycle IVF was equivalent to one cycle of conventional IVF (but there was less stress and natural cycles were much safer).

Dr. Daiter’s review of this chapter

The authors are from the New Hope Fertility Center’s Mexico IVF Center.  New Hope Fertility Center in NYC is a world renowned IVF center that offers many of the newest approaches and protocols for IVF.

In the USA there are few IVF centers that offer or encourage the use of natural cycle IVF and conventional IVF is currently so expensive in the USA that it is often not available for infertile couples without medical insurance coverage.  Additionally, many couples with decreased ovarian reserve or advanced reproductive age are not offered conventional IVF without the use of donor eggs.  This chapter points out that these are ideal patients to consider for natural cycle IVF, and where this treatment is perfectly appropriate if the couples chose it once they understand the risks,  benefits and alternatives.

Techniques and protocols that improve the endometrial receptivity (including the use of cryopreservation via vitrification) and limit the loss of cycles due to premature LH surges or premature ovulation are constantly being developed and should improve overall success with natural cycle IVF.

I believe that one should applaud the research efforts involving non-conventional IVF throughout the world.

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