In Vitro Maturation, (IVM), is a process by which immature oocytes are harvested from the ovaries and cultured in the laboratory to a mature stage. The mature oocytes are then fertilized by intra-cytoplasmic sperm injection. After the eggs are fertilized, they are cultured further in the laboratory into fully developed embryos suitable for transfer.
Immature Oocyte at Germinal Vesicle Stage
Immature Oocyte at Metaphase I Stage
Mature Human Oocyte
The first in-vitro fertilization, (IVF), baby was born in 1978 in a spontaneous cycle. In the first few years when IVF was done, no fertility drug was used. The live birth rate was less than 10% per cycle. Fertility drugs such as clomiphene citrate and later gonadotropins were added to IVF treatment to stimulate the ovaries so as to increase the success rate. The major benefit of fertility drugs is to increase the number of mature follicles, or super-ovulation. More mature follicles lead to more eggs retrieved and consequently more embryos created. When multiple embryos are produced, the odds of identifying one or two normal embryo(s) to transfer leading to a live birth would be proportionately increased. Overwhelming majority of all IVF performed in the world uses ovarian stimulation.
In addition to the added cost, use of fertility drug such as gonadotropin is associated with possible risk of ovarian hyper-stimulation syndrome, OHSS, a potentially life-threatening side effect. The risk of severe OHSS is about 0.2% of all treatment cycles. Women with polycystic ovarian syndrome, (PCOS), are especially prone to develop severe OHSS. Several effective strategies are available to avoid OHSS. IVM is one such strategy. Recent advances in culture condition allowed more effective growth of immature oocytes in the laboratory, making IVM a realistic option.
In a typical IVM cycle, no ovarian stimulation is used, although low dose gonadotropins are used by some. Hence the benefits of IVM are
- avoidance of the side effect of fertility drug and
- reduced cost of treatment
As in the case of regular IVF, pregnancy rate in IVM is directly proportional to the number of oocytes retrieved and the number of embryos available for transfer. On average, only half of all immature oocytes retrieved can be cultured to maturity successfully in the laboratory. For reasons that are still unclear, the implantation rate per embryo is about 10% lower in IVM than in IVF. So generally this is compensated by transferring an additional embryo. So in order to have three (3) good quality day 3 embryos to transfer, one must have at least 5-6 mature oocytes.
Young women with PCOS typically have numerous small follicles within the ovaries, allowing a large number of immature oocytes to be retrieved and cultured to maturity in the laboratory before they are fertilized. The ideal candidates for IVM are:
- women younger than 35 years of age
- has PCOS
- PCO like ovaries, i.e. more than 12 small antral follicles
Clinical pregnancy with IVM for this group of women can be as high as 25-35% per cycle. Other non –PCOS patients who may benefit from IVM are:
- Women who want to undergo a “natural-cycle” IVF procedure by avoiding stimulating hormones
- Women wanting to avoid the potential risk of fertility drug use such as OHSS
- Fertility preservation for women about to undergo radiation or chemotherapy treatment for cancer and do not have the time to undergo gonadotropin stimulation protocol
- Patients having undergone repeated stimulation cycles with no success
At the Family Fertility Center, we offer IVM primarily for PCOS women who failed to ovulate with clomiphene citrate. We also extend IVM to non-PCOS patients as described above. IVM has its merits but is not for everyone. The advantages of IVM have to be balanced against its lower per cycle success compared with conventional IVF, especially for younger women with no PCOS and normal ovarian reserve. The lower cost of IVM, because no fertility drug is used, can be offset by the increased number of cycles of treatment in this group of patients. Conventional IVF among these women have a live birth rate as high 50%-60% per fresh cycle. Many of these women have extra good quality embryos to freeze and allow more chance to conceive in a frozen embryo transfer.
The long term effect of culturing immature oocytes in the laboratory, as opposed to its “natural” environment in the ovary, is largely unknown. IVM, compared to IVF, adds an extra day or two of culturing the eggs in the “artificial” conditions of an IVF laboratory. Imprinting [“Genomic imprinting is a phenomenon in mammals where the father and mother contribute different epigenetic patterns for specific genomic loci, or location, in their sperm cells or egg cells.”] disorders, such as Angelman syndrome and Prader-Willi syndrome, although rare in the general population, are found to be more prevalent among babies born as a result of IVF. Some had speculated that the prolonged culturing of embryos in the laboratory exposed them to artificial conditions which might be the cause of epigenetic [“Epigenetics refers to the reactions and factors that influence gene control, the switching on and off of individual genes at strategic times and locations caused by mechanisms other than changes in the DNA sequence.”] changes. Such epigenetic changes then lead to the increased prevalence of such imprinting diseases among IVF babies. Would the prolonged culturing of eggs in the laboratory further increase the risks of epigenetic changes in these embryos? More research is needed in this area.