Dominant Follicle Diameter Helps Select Optimal Day for Oocyte Retrieval in IVM Cycles

In vitro maturation (IVM), a novel assisted reproduction technique, reduces risks associated with in vitro fertilization (IVF) as the eggs are retrieved, matured and fertilized in vitro prior to implantation, thereby eliminating ovarian stimulation. However, the factors predisposing the success or failure of IVM cycles are unclear. Now, a recent study published in the December issue of the journal, Human Reproduction suggests that dominant follicle (DF) size of ≤14mm at oocyte retrieval following human chorionic gonadotropin (hCG) priming improves pregnancy outcomes in cycles programmed for IVM treatment.
Weon-Young Son from the McGill University, Montreal, and coworkers conducted a study on 160 women with polycystic ovaries (171 cycles) to compare the DF size at oocyte retrieval after hCG priming with IVM outcome. When the endometrial thickness reached a minimal of 6 mm, the researchers subcutaneously administered 10,000 IU hCG, 35 to 38 hours prior to oocyte collection. The retrospective analysis was performed in 3 study groups based on the DF diameter: group 1, with a diameter of ≤10 mm; group 2, between 10 and 14 mm; and group 3 of >14mm. In the corresponding 3 groups, 6.9%, 10.6%, and 15.1% of the in vivo matured oocytes were collected, suggesting a positive correlation between the size and number of oocytes.
Results showed that among the sibling immature oocytes extracted in the 3 groups, the rates of IVM, fertilization and embryo development were similar. It was found that group 3 exhibited a lower clinical pregnancy rate (17.1%) compared to group 2 (40.3%). Furthermore, groups 1 (13.6%) and 2 (14.3%) had higher implantation rates than group 3 (4.9%). Based on the study findings, the researchers proposed DF ≤14mm as the optimal oocyte retrieval time for IVM cycles, as DF >14 mm may detrimentally affect the sibling immature oocytes.
Earlier, the same group of researchers conducted a retrospective study (Human Reproduction, 2008) to investigate if an extension in the time interval between hCG priming and immature oocyte retrieval enhances the oocyte maturation rate after IVM. The assisted reproduction technique was performed on 113 polycystic ovary syndrome patients (120 cycles) and the oocytes were collected at either 35 hours (group 1=76) or 38 hours (group 2 = 44) following 10,000 IU of hCG priming. The oocyte maturity was analyzed after the retrieval and the culture of the immature oocytes was performed till day 2 using IVM medium. It was found that the number of in vivo matured oocytes was considerably lower in group 1 (13.6%) compared to group 2 (7.3%). Also, group 2 exhibited a higher oocyte maturation rate after day 1 (46.3 vs. 36.0%), clinical pregnancy (40.9 vs. 25%) and implantation rates (15.6 vs. 9.6%) than group 1. Based on the findings, the scientists suggested that extending the time of hCG priming from 35 hours to 38 hours for oocyte retrieval could improve the pregnancy outcome of IVM cycles.
In vitro maturation of immature oocytes collected from unstimulated ovaries is an assisted reproduction technology that is extensively being studied. Some of the advantages of IVM over IVF are that it is less expensive, has shorter treatment regimen, and does not require the use of hormonal fertility drugs for ovarian stimulation. It may thereby eliminate the risk of developing ovarian hyperstimulation syndrome and multiple pregnancies.
Several previous studies have indicated that controlled ovarian stimulation in combination with in vitro fertilization cycles provide better results compared to in vitro maturation techniques. Now, the identification of the optimal hCG priming time and dominant follicle size for oocyte retrieval may help in enhancing the success rates of the novel IVM technique with fewer adverse effects compared to IVF.
References
1.Son WY, Chung JT, Herrero B, et al. Selection of the optimal day for oocyte retrieval based on the diameter of the dominant follicle in hCG-primed in vitro maturation cycles. Hum Reprod. 2008 Dec;23(12):2680-5. Epub 2008 Sep 4.
2.Son WY, Chung JT, Chian RC, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008 Sep;23(9):2010-6. Epub 2008 Jun 12.

A Cheaper Alternative To IVF

A landmark in the development of fertility treatment was announced by doctors yesterday with the birth of the first babies to be conceived using a revolutionary technique that offers a safer, cheaper alternative to IVF. The twin boy and girl, who were born on 18 October at the Radcliffe Infirmary in Oxford, were conceived using In Vitro Maturation (IVM), a method that dispenses with the use of costly fertility drugs, saving up to £1,500 (INR 120,000) on the normal price of treatment. The technique is also safer for the one in three women among those seeking fertility treatment who have polycystic ovaries, a condition that puts them at high risk of dangerous side effects from fertility drugs. Specialists said the development could make in vitro techniques available to more infertile couples by cutting the cost of treatment. Infertility is estimated to affect one in six couples in the UK but IVF costs around £5,000 (INR 400,000) a cycle and treatment is restricted on the NHS!

Tim Child, a consultant gynaecologist at the Oxford Fertility Clinic and senior fellow in reproductive medicine at Oxford University, who led the work, said: "I think it is a safer, cheaper alternative to IVF for all women. However, for many women the success rates are currently much lower. Research in the future will address this." The Oxford Fertility Clinic is the only one in the UK licensed to use the technique: 20 cycles of treatment have been carried out and four other women are currently pregnant, giving a pregnancy rate of 25 per cent. This is expected to improve with further experience. In addition, without the need for drugs, repeating the procedure would be less taxing on the woman. For standard IVF, the Oxford clinic's pregnancy rate is 45 per cent.

The parents of the babies, who have asked to remain anonymous, were delighted, Mr Child said. At birth the boy, born first, weighed 6lb 11oz and the girl weighed 5lb 14oz. "The parents are ecstatic. They have got absolutely stunning twins. They went home on Tuesday to start their new life together. It is wonderful."

In standard IVF, the woman takes fertility drugs for five weeks to stimulate production of her eggs, which are then collected direct from her ovaries under the guidance of ultrasound, before being fertilised in the laboratory. The drugs cost between £600 and £1,500, with charges often higher in London. The procedure is time consuming and uncomfortable and for the third of women with polycystic ovaries there is a one in 10 risk of severe ovarian hyperstimulation syndrome, a dangerous side-effect that in rare cases can prove fatal.

IVM avoids the use of drugs and instead involves collecting eggs from the ovaries while they are still immature. The eggs are then grown in the laboratory for 24 to 48 hours before being fertilised and replaced in the womb. The technique was pioneered by the University of McGill in Montreal, Canada, where Mr Child spent two years researching and developing it before joining the University of Oxford in 2004. It has also been used in Seoul, South Korea, and Scandinavia. To date about 400 babies have been born worldwide using IVM compared with around two million by IVF. At present the Oxford Fertility Clinic is only offering the treatment to women with polycystic ovaries, but in the long term Mr Child said he hoped to offer the procedure to all women. "When we see patients we say these are the options and it is up to them to decide. We are not offering it to women with normal ovaries at present because we don't get enough eggs from them. It depends on the number of resting follicles and with normal ovaries you don't get so many.

"On average we get four eggs from a woman with normal ovaries compared with 16 from one with polycystic ovaries. The procedure involves a process of attrition – two-thirds mature and two-thirds of those fertilise – so you need a decent number to start with." Research on developing the culture medium in which the eggs are matured in the laboratory could reduce the attrition rate so that fewer eggs are needed. The technique could then become suitable for women with normal ovaries, Mr Child said.

A second drawback of the procedure was that eggs grown in culture had a harder outer shell than those matured in the ovary and were more difficult for sperm to penetrate. The eggs had to be fertilised by ICSI – injecting a single sperm directly into the egg. "We hope to develop the culture medium so the egg doesn't mind being grown in the laboratory and we can use ordinary insemination [mixing eggs and sperm so fertilisation occurs naturally]. But in most IVF clinics, 50 per cent of patients are treated with ICSI anyway," he said. "Anything that reduces the cost of IVF, provided it is safe, means treatment could be available to more people. But this is an emerging technology – it is very early days. The most important thing is that patients get proper information so that they can make a decision on what is best for themselves."