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Our path to developing an in vitro maturation (IVM) program

How to choose an in vitro maturation (IVM) program

A patient recently asked me to describe what training I had had in IVM. I related what I had done over the last few years to develop our IVM program, but realized that this patient’s question was really the more difficult one of how to evaluate and compare the programs that perform in vitro maturation.

First of all, it is difficult to even find a program experienced in doing in vitro maturation. We have been doing in vitro maturation for only four years, yet I don't know of any programs in the United States that have a larger experience than us. In the context of the world, there are a number of programs that I can name, but in the United States, IVM has not yet caught on.

United States IVF data reporting (mandated legally through the Center for Disease Control) does not separately report the results of IVM cycles.  The CDC clollects and excludes them.  SART collects and mixes the results in with conventional IVF data. There is no standardized reporting method in the United States that provides any information about IVM. (Europe is a bit better.) Different programs use different criteria for choosing patients to undergo IVM, but the majority are younger women (ages under 30, 35 or 38 are the usual cutoffs) with a large number of visible small cysts in their ovaries on ultrasound (high antral follicle count). Most of these patients have some variant of polycystic ovaries (PCOS).  Oxford University published results on a series of patients treated with IVM who did not have PCOS.

Success rates and other assessments with in vitro maturation should use similar patients undergoing conventional IVF as a basis for comparison. Given the small number of patients undertaking IVM, this is very difficult to do. Patients with PCO generally do better with conventional IVF than patients doing IVF for other reasons. They also have more side effects from the medications and are the subgroup of patients at greatest risk for severe ovarian hyperstimulation syndrome.

Our approach is to recommend IVM (or Mini-IVF) to patients who have failed to get pregnant after using oral medications and IUI.  Patients who fail IVM can then go on to IVF.  IVM is thus advocated as  an intermediate therapy which can save a majority of people from the more expensive and uncomfortable conventional IVF cycles.

In our program (with patient numbers too small for statistical certainty), the ongoing pregnancy rate with IVM is slightly lower than the ongoing pregnancy rate for age matched patients undergoing conventional IVF. The “ovulation induction process” is much easier for patients with IVM than with conventional IVF. There are many fewer side effects of medications with IVM. The cost to the self-pay patient for each pregnancy achieved is about half of that for conventional IVF in our program.  This make IVM more cost effective (in several ways) than traditional IVF for this patient population.

A physician friend asks, “What is your secret?” There is no secret. The general outline of doing IVM is well established as it uses components of conventional IVF. The details of patient management are still evolving, but there is no single detail of overwhelming importance.

The evolution of our program

After learning that the IVF media company, Sage, had a commercially available media for in vitro maturation which it had licensed from the group at McGill, I became interested in IVM in 2009. My initial interest in IVM was to try to find a lower cost method of IVF that I could use for my patients.

Sage offered an individualized course in the use of its media, which was taught by Dr. Jared Robbins at Brown University. I observed Dr. Robbins undertake an IVM retrieval, observed how the laboratory did IVM, and had Dr. Robbins present his approach to IVM to me. I then undertook Dr. Robbins’ very structured approach to IVM at Infertility Solutions, P. C. and had our first pregnancies rather quickly.  (Dr. Robbins excellent results have recently been published.)

I next had the opportunity to spend a week with Dr. S. L. Tan’s group at McGill in Montreal. McGill has been doing IVM for more than ten years. Many physicians and embryologists who do IVM elsewhere in the world have spent time there and it remains one of the premier institutions to go to for training. Their clinical results are excellent and they have published extensively about IVM. I spent time with physicians Dr. S. L. Tan and Dr. H. Holzer and with embryologists Dr. W. Y. Son and Dr. R. Chian (the primary developer of the media produced by Sage.) They generously shared information about IVM both formally and informally and in laboratory and the operating room. I returned to Allentown and found ways to incorporate their ideas into my patient management and our program improved.

My next opportunity for academic enhancement occurred when I attended the second international IVM conference in Milan, Italy. This conference brought clinicians, embryologists and basic scientists together to share the latest information on in vitro maturation.

The conference exposed me to a number of new ideas as well as introduced me to many large IVM programs across the globe. I realized that as a reproductive endocrinologist, my education in ovarian physiology had focused on the two week period of time during which selectable follicles developed, eggs became mature and the eggs ovulated. These are the times of key intervention in infertility and IVF therapy. However, I knew almost nothing about the five months during which eggs developed from primordial follicle into selectable follicles. I returned home with the objective of trying to understand this time period in ovarian physiology in ways that I could apply to the clinical part of in vitro maturation.

Our program continued to improve. One of the objectives I had long harbored was to increase my egg yield during egg retrieval. I learned that Dr. Peter Hans-Steiner had developed a very thin needle that used a new technique to enable possible flushing of the very small follicles used for in vitro maturation. He invited me to visit him at his office in Ganz, Austria and observe his retrievals using this Steiner-Tan needle. It was a great innovation. I found it made the IVM retrieval process easier and, with the large amount of flush media used, it also made the search for eggs in the laboratory easier. We have not yet done enough cases to make a comparison, but it seems we have improved our egg yield which should improve our pregnancy rate.

After performing IVM for two years, I realized that our program had uncovered insights about IVM that were not in the published literature and might help other physician wishing to undertake IVM.  Careful evaluation of the existing medical literature when you choose to publish something is often a valuable experience.  Presently, ten papers dealing with some aspect of IVM have come out of our program and have been accepted by peer reviewed medical journals.

Our IVM program has reached the point where it provides a unique opportunity for patients. For the patient under 35 with PCOS, who failed to get pregnant using clomid and IUIs, I would strongly recommend it over IVF. It is easier, has less risks and side effects and is less expensive for the patient than conventional IVF. Yet, our program is still evolving. We learn from our patients and their responses. I don’t expect this to change any time soon.