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NHK World-Japan:
Reawaken the Ovaries to Give Birth


What is IVA?

IVA, short for In Vitro Activation, is a new procedure to obtain mature eggs from women in which ovarian pieces are activated outside the body before grafting back to patients. It was featured as one of TIME magazine's Top 10 Medical Breakthroughs of 2013.

For a pregnancy to take place, one egg from mother needs to be fertilized by sperm from father. Inside women's ovaries, there are many follicles, each containing an egg surrounded by supporting cells. At birth, ovaries contain about 800,000 follicles in girls and, after puberty, one follicle per month reaches the mature stage and releases a mature egg. During a woman's reproductive life, only about 400 follicles reach the mature stage. Because the total number of ovarian follicles in women is fixed at birth, the number of available follicles (or ovarian reserve) decreases with age. Some women experiences 'diminishing ovarian reserve', resulting in infertility.

For women suffering from diminishing ovarian reserve and infertility, no mature follicles containing eggs are present. However, some patients still have residual small follicles in their ovaries with the potential to grow into mature ones and release mature eggs, leading to pregnancy.

Using the IVA approach, the doctor retrieves one ovary from patients using laparoscopic surgery. Using a miniscule amount of ovarian tissue, the presence of follicles is determined. The majority of ovarian tissues are frozen for later activation. When follicles are detected, the doctor informs the patient and activates the "sleeping" follicles by treating the thawed ovarian tissues with IVA drugs. After two days, ovarian pieces are grafted back to the patient near the oviduct under laparoscopic surgery and follicle growth will be monitored biweekly using ultrasound and serum hormone levels. When follicles reach the mature stage, mature eggs will be retrieved for fertilization with husband's sperm in the laboratory to generate early embryos for freezing. Patient will be treated with hormones to prepare the uterus for embryo implantation. When the uterus is ready for implantation, the doctor will thaw the embryos and transfer them back to the patient for pregnancy.

A simplified Drug-free IVA procedure has been developed recently for POR (Poor Ovarian Response) patients by Dr. Kawamura. POR patients responded to traditional FSH stimulation with the growth of less than five follicles instead of the usual 20 to 30 follicles. This drug-free IVA approach omits the two-day drug treatment of ovarian pieces and involves only one laparoscopic surgery. A small piece of ovary was obtained under surgery and cut into pieces in the lab before immediately putting back to patients’ ovaries. Following hormonal treatment, growth of many follicles in many growth waves could be found in most POR patients to allow natural conception, artificial insemination of sperm, or egg retrieval for IVF and embryo transfer.