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In Vitro Maturation – IVM

In vitro fertilization has helped hundreds of thousands of couples to achieve pregnancy and live births. Although initial efforts at in vitro fertilization in the 1960s attempted to mature eggs in the laboratory, these techniques were largely unsuccessful. The first live birth from in vitro fertilization obtained a single egg that was matured inside the ovary. No fertility medications were used. This “natural cycle” in vitro fertilization was gradually replaced by “stimulated” in vitro fertilization using various fertility medications since it was shown that when a larger number of eggs were retrieved, a larger number of embryos could be created. This allowed for selection of the best embryos for transfer into the uterus and as a result – pregnancy rates improved.

However, the use of fertility medications for ovarian stimulation has become extremely expensive. In addition, some women are extremely sensitive to the effects of these medications and, as a result, can develop a potentially life-threatening condition known as ovarian hyperstimulation syndrome (OHSS). Finally, there are some women who have cancers that are hormonally responsive and therefore must avoid the high hormone levels that result from ovarian stimulation.

Clearly, there is a great need to develop better techniques to perform in vitro fertilization without the use of fertility medications. In 1991, physicians in Korea reported the first pregnancy from eggs that were obtained from an ovary at the time of a cesarean section and then matured in the laboratory. In 1994, another pregnancy was established in Australia using immature eggs that were obtained from women with polycystic ovary syndrome.

Recent improvements in culture conditions and techniques have led to a great improvement in the likelihood for in vitro matured eggs to produce viable embryos.

In vitro maturation candidates

The best candidates for IVM (in vitro maturation) are young women with large numbers of egg containing follicles or women who have attempted stimulated in-vitro fertilization and had production of a large number of eggs.

 

Ideally, women under the age of 30 or 35 would be expected to have the greatest likelihood for having many eggs.

 

There are two tests that are used to identify women with a large number of eggs. Using vaginal ultrasound, the ovaries can be seen and the egg containing follicles can be counted for each ovary. An excellent number of follicles to be a great IVM candidate would be more than 15 follicles in each ovary. A blood test can also tell about the number of eggs in the ovaries. A hormone called AMH (anti-mullerian hormone) is produced by follicles in the ovary. A higher AMH level indicates a larger number of eggs in the ovaries. AMH levels will vary by age. As women get older and the number of eggs in their ovaries decrease, the AMH levels will start to decrease. For IVM, a woman should have an AMH level in the upper half for her age group.

 

Women who are obese are not good candidates for IVM. The ovaries are very small when they are not first stimulated by fertility medications. This makes them more difficult to see on ultrasound. Obesity also makes it more difficult to see the ovaries on ultrasound and therefore makes it more difficult and more risky to try to remove the eggs from the ovaries.

 

Women who have taken injectable fertility drugs previously and who had a very vigorous response or had a treatment that was cancelled for fear of hyperstimulation syndrome, may be very good candidates for IVM.

In vitro maturation techniques

The technique involved for in vitro maturation begins with a woman having a transvaginal ultrasound performed between day 3 and 5 of her menstrual cycle. If she does not have evidence for regular menstrual cycles and natural ovulation, she would be a candidate for in vitro maturation alone. If she has regular ovulatory cycles, then she is a candidate for natural cycle in vitro fertilization combined with in vitro maturation.

 

An injection of hCG is given and the eggs are retrieved 36 hours later. The immature eggs are placed in a petri dish containing specialized media to help the eggs mature. Once the eggs are matured, they are injected with sperm – this is a fertilization technique known as ICSI . The injected eggs are now cultured for several additional days to allow the embryos to develop. This is the same technique that is used in standard in vitro fertilization.

During this time, the female is given hormones to prepare the uterine lining. Both estrogen and progesterone are given after the eggs have been retrieved.  A few embryos are then selected and an embryo transfer is performed.

In vitro maturation results

A recent series from a fertility group in Canada followed the treatments of 63 women without ovulatory cycles. The average age of the women was 31. An average of 16 immature eggs were collected. Of these, about 65% could be matured in the laboratory. 79% of the eggs which matured were able to be normally fertilized by injection of a single sperm into each egg (ICSI). 90% of the fertilized eggs began to divide. If a patient had viable embryos for transfer, approximately 30% had a live birth. This is significantly lower than the pregnancy rate that can be achieved with stimulated in vitro fertilization, however, it is similar to what is seen using injectable fertility medications and intrauterine insemination.

Women who had ovulatory cycles are first monitored until they are though to be at a point just before ovulation. This enables the physician to potentially obtain one or two mature eggs in addition to the immature eggs. Using this technique, a similar live birth rate was obtained by the same Canadian group.

As with all fertility treatment, success rates are lower for older women. Using in vitro maturation, the pregnancy rates for women above age 35 were very low. Thus these women are not good candidates for this technique.

Last year, IVF1 became the first fertility center in the United States to achieve pregnancy using IVM.