Treating some women with a procedure known as in vitro maturation (IVM) combined with "natural cycle" in vitro fertilization (IVF) might be a new, feasible way to help women conceive, says a new study.1
IVF Alternative
In vitro maturation is a procedure in which harvested eggs are matured in a laboratory, rather than allowing them to mature naturally in the body.2 The pregnancy rate using IVM is about 30% to 35% per embryo transfer, explained study leader Ri-Cheng Chian, PhD, in the department of Obstetrics and Gynecology at Royal Victoria Hospital in Montreal, Canada, in an interview with Priority Healthcare.
"In comparison with conventional IVF, the major advantages of IVM treatment include avoidance of the risk of ovarian hyperstimulation syndrome, reduced cost, and simplified treatment," wrote Chian and colleagues in a review paper on the topic last year.3
For women planning to undergo in vitro fertilization, a typical treatment cycle begins with a protocol of medications aimed at artificially inducing ovulation. But Chian's team writes that this treatment protocol known as controlled ovarian hyperstimulation (COH) can cause side effects like ovarian hyperstimulation syndrome, a condition in which too much abdominal fluid builds up. Symptoms can range from moderate to severe.
Although COH has gained popularity since IVF was first introduced in the late 1970s, "there has been a resurgence of interest in natural-cycle IVF treatment in recent years because of the increased efficiency of IVF technology" that has resulted in improved egg retrieval outcomes, wrote Chian's group. Due to those higher success rates, natural-cycle IVF is likely to "become a more common approach in the future," said Chian, who is Scientific Director of the McGill Reproductive Center at Royal Victoria Hospital.
It's also been shown previously that retrieving immature eggs, then using IVM to mature them in the lab before inseminating them with sperm using intracytoplasmic sperm injection (ICSI) is feasible for women with polycystic ovary syndrome (PCOS), the researchers noted. But IVM is not designed solely as an option for PCOS patients, said Chian. "This procedure can be used for all infertile women with all types of causes," he told Priority Healthcare.
Successful IVM Outcomes
Chian's team described three case reports in which IVM combined with subsequent IVF was successful at their hospital.
Each of the patients underwent "natural cycle" IVF combined with IVM. The first patient had a 5-year history of infertility. "She had failed to become pregnant after 6 cycles of conventional IVF treatment over the preceding 3 years," Chian's team wrote.
In this case, doctors found a dominant follicle on day 8 of her natural menstrual cycle, and a human chorionic gonadotropin (hCG) was given to trigger ovulation two days later. Several eggs were retrieved, and physicians checked for their maturity level. Two of them were found to be immature, and they underwent IVM for 2 days. "Intracytoplasmic sperm injection was performed for insemination because we believe that ICSI can result in a higher fertilization rate than conventional IVF," Chian's group wrote.
Sixteen hours later, two embryos were confirmed and were subsequently transferred to begin pregnancy. Physicians gave the patient estradiol, and for luteal support, also gave progesterone doses to help boost the odds of a successful implantation. Six weeks later, the woman became pregnant, and later gave birth to a healthy baby boy.
PCOS Patient Treated
In the second case, a woman who appeared to have PCOS and had previously given birth to an infant using IVM had had difficulty conceiving despite two IVF attempts.
After discovering a dominant follicle in the patient on the 8th day of her menstrual cycle, she was given hCG to trigger ovulation 36 hours before egg retrieval. A total of 10 eggs were collected, eight were found to be immature, and they subsequently underwent IVM. Two of them were matured for 6 hours, and the remaining 6 eggs, which were found to be very immature, underwent IVM for an additional 48 hours.
Eventually, 4 eggs were fertilized, after all of them underwent IVF/ICSI, and three of them were transferred after it was determined that the fourth embryo had not matured properly and was not suitable for freezing.
Six weeks later, pregnancy was confirmed on ultrasound and the woman gave birth to a healthy infant girl.
Another PCOS Case Treated
In the final case cited, the investigators describe a woman who was not able to ovulate and had been diagnosed with PCOS. The patient had irregular menstrual cycles and a 3-year history of infertility. After unsuccessfully attempting pregnancy with 6 cycles of intrauterine insemination (IUI), she decided to undergo a different treatment protocol. Doctors gave her doses of progesterone once per day for 10 days to help induce withdrawal bleeding. They observed no ovarian cysts after performing an ultrasound scan after progesterone therapy. After observing a dominant follicle in the patient, they gave doses of hCG to trigger ovulation.
On the woman's 10th day of her cycle, 17 eggs were collected—12 of them immature. While five immediately underwent ICSI, the 12 immature eggs underwent IVM—7 of them for 24 hours, and the rest for 2 days. Those that had reached maturity subsequently underwent ICSI.
Physicians found that 10 of the eggs had fertilized, and four of them were transferred for pregnancy. Five additional eggs were frozen for later use. Six weeks later, doctors confirmed the woman's pregnancy. "At the time of submission of this report, the patient had a 17-week ongoing pregnancy," Chian's team wrote.
Based on these case studies, Chian and his colleagues speculate that IVF combined with IVM is a "potential treatment for women with various causes of infertility."
Rethinking a Protocol
The researchers say it was policy at their hospital to not perform IVM if a dominant follicle was observed in patients because it was thought that this follicle suppresses the remaining small follicles. But these case studies show that that is not necessarily the case, they write. Although immature eggs are frequently retrieved from larger follicles, these case studies suggest that immature eggs can also be collected from smaller follicles.
"There is an increasing interest in natural-cycle IVF among patients because it is simple, quick, and avoids the side effects with ovarian stimulation," they wrote. "Some patients might prefer to undergo a number of successive natural IVF treatment cycles instead of having a single stimulated IVF cycle, which can only be repeated once every few months."
While the odds of successfully retrieving multiple eggs and creating embryos are lower in natural-cycle IVF, "an attractive possibility" would be to enhance the success rate by combining IVF with IVM of immature eggs collected, the study team wrote.
They advocate future clinical trials to determine the best way to design a treatment protocol with the aim of synchronizing uterine receptivity for implantation with embryo development. This would "optimize the implantation rate", they noted.
1. Chian RC, Buckett WM, Jalil AKA et al. Natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes is a potential approach in infertility treatment. Fertil Steril 2004 Dec;82(6):1675-8.
2. Hreinsson J, Fridstrom M. In vitro oocyte maturation for safer treatment of infertility. The risk of ovarian overstimulation syndrome is minimized [Translated from Swedish]. Lakartidningen 2004 Nov 11;101(46):3665-8,3671.
3. Chian RC, Lim JH, Tan SL. State of the art in in-vitro oocyte maturation. Curr Opin Obstet Gynecol 2004 Jun;16(3):211-9.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
