Our 12th case study deals with a couple who lived abroad in Saudi Arabia and wished to come to SIRM-Las Vegas for IVF with egg donation. They had a history of five prior IVF failures using her own eggs. The husband had a very hectic and busy professional schedule. Thus, they wanted to optimize convenience, minimize the time away and to do so with as little hassle as possible, without increasing cost and without compromising success. I proposed a novel approach to egg donor IVF which achieves all these objectives: “Staggered IVF” using CGH for embryo selection, all done at a distance. This approach separates the egg donor cycle from the embryo transfer cycle and allows the recipient couple to plan for a time when they will have to spend less than half the usual time period away from home. I have highlighted the process in this post.

Background: Fatima, a 42 year old woman and her perfectly fertile male partner, Mohamed, had been trying to conceive through in vitro fertilization (using her own eggs) for approximately 4 years. During that time they had undergone 5 failed IVF attempts. Largely due to a combination of advancing age and diminishing ovarian reserve (her most recent FSH on day 3 was 17.1 mIU/ml and her AMH levels were 0.2), Fatima had been unable to propagate good quality eggs or embryos. With this in mind, they elected to come to SIRM-Las Vegas for IVF with egg donation.

The Problem: This couple lived in the Middle East (Saudi Arabia), and were both very busy professionals. For this reason, having to travel all the way to Las Vegas and spend up to 2 weeks away from home and work, posed a significant problem. Moreover, they were concerned about the possibility (albeit unlikely) of making the long journey and spending significant time away from home, only to find that there were no good quality embryos available for transfer, thus making their entire investment in time, money and emotion for naught.

The Solution: I presented the couple with the option of doing “Staggered IVF with Egg Donation at a Distance” and using CGH for embryo selection. Using this approach, they would not even have to leave home for the United States until they were assured of having “competent” embryos available for transfer. Because they were using donor eggs, Fatima would not need to be at our clinic until shortly before the embryo transfer. Moreover, the date they would have to arrive in Las Vegas would be chosen to meet their convenience and would be known to them well in advance allowing them to arrange their schedules conveniently. In all, the time spent with us would be less than a week. Finally the process of CGH embryo selection would afford them about a 70% chance of success.

Why Staggered IVF with Egg Donation is a Preferred Option for Couples Traveling from a Distance
This option involves separating the cycle of donor stimulation, retrieval and fertilization, from the cycle in which the recipient undergoes embryo transfer. Needless to say, the partner’s sperm must be available at the time of the donor egg retrieval, but this rarely presents a problem, since arrangements can almost always be made to have a frozen (cryopreserved) sperm sample forwarded to us well in advance of the retrieval.

The donor egg retrieval is thus usually performed while the recipient couple remains at home awaiting a report on the number and quality of embryos generated through IVF. In many instances (as was the choice in the case of this couple), we take embryo selection beyond the level of defining embryo “competency” on the basis of development to the blastocyst stage. Instead, the couple wisely decided to biopsy all viable embryos and to test them for their chromosomal integrity using metaphase CGH.

This approach of Staggered IVF with Egg Donation is ideally suited to meet the needs of busy couples, especially those who plan on traveling out of their area for IVF with egg donation.

• It should be clarified that with the introduction of ultra rapid embryo freezing (vitrification), the embryos are not adversely affected. More than 95% will survive the freeze/thaw and upon being transferred will have at least as good a chance at propagating a viable pregnancy as do their fresh (non frozen) counterparts. This is in stark contrast to what used to be the case when conventional (slow) freezing was used to store embryos. The slow cooling-down process led to ice crystal formation within the cells of the embryos, thereby damaging many of them. This reduced their post-thaw survival and resulted in poor pregnancy rates.Conversely, with vitrification, the embryo is frozen about 600 times faster…so fast that it prevents ice crystal formation. The embryos are thus not damaged and survive the thaw in prime condition. Furthermore, the baby rate per thawed blastocyst using this freezing method is no different than is the case for freshly transferred blastocysts.
• Since blastocyst vitrification does not harm the embryos significantly, it is possible to hold them in cryostorage for as long as needed without prejudice. Thus, recipients can avoid the complexities and inconvenience of having to be present in tandem with the egg donor during the cycle of IVF. Not only is this more convenient, but it prevents the recipients from inadvertently coming into contact with the otherwise “anonymous” egg donor. It also allows the luxury of scheduling the embryo transfer procedure to meet the needs of their calendar. Finally, it reduces the required time away from home by at least half.
• I have previously alluded to the fact that embryos that fail to progress to the blastocyst stage are almost always chromosomally abnormal (aneuploid and “incompetent”) and thus not viable for transfer. The old adage that transferring embryos earlier on into the uterus would provide a more favorable environment for their development is fundamentally flawed. There is simply no evidence to support this contention.Furthermore, by allowing embryos to progress to the blastocyst stage, many of the aneuploid (“incompetent”) ones will be culled out along the way. The addition of CGH embryo selection further refines the process of eliminating those embryos that have no chance of developing into viable pregnancies. Thus, one can improve the pregnancy rate dramatically by transferring even a single CGH-normal blastocyst, and in the process avoid the temptation of transferring numerous embryos with the risk of high order multiple gestations (triplets or greater) and all its associated hazards.

Selecting an Egg Donor: We proceeded to help the couple identify a suitable egg donor through a Las Vegas-based third party parenting agency “Footsteps to Family” (www.footstepstofamily.com). Five potential egg donor candidates were identified. They ultimately settled on Claire, a 29 year old single woman who had a proven track record – with a successful pregnancy in one of my patients approximately 2 years prior. We arranged to have a cryopreserved specimen of Mohammed’s sperm sent to us.

The Egg Donor’s IVF Cycle: The egg donor underwent controlled ovarian stimulation (COS) and egg retrieval (ER). She produced 19 mature eggs (MII’s) These were fertilized using intracytoplasmic sperm injection (ICSI) resulting in 13 morphologically sound day-3 embryos that were all biopsied for CGH testing. Eight progressed to the expanded blastocyst stage and were promptly vitrified and cryobanked. The biopsied DNA specimens derived from those embryos that had developed into blastocysts were sent out for metaphase CGH testing, where it was determined that four (4) were chromosomally normal (euploid) and thus likely to be “competent”.

Preparing the Recipient (Fatima) for a Frozen Embryo Transfer (FET): At this point, the couple set a date to travel to the US (Las Vegas) for an embryo transfer two months later, at a time that would be most convenient for them. The plan was to transfer 2 CGH-normal embryos to her uterus. Fatima went through a screening process at home in Saudi Arabia, based upon guidelines set by us and overseen by her SIRM Clinical Coordinator. This preparation included general medical clearance (physical examination, EKG, chest x-ray, mammogram and blood testing). Fatima had her uterine cavity evaluated by saline sonography (sonohysterogram) and we arranged for her to have a blood sample sent to Reproductive Immunology Associates (RIA) in Van Nuys, CA for an alloimmune and autoimmune evaluation. This would help to exclude an underlying immunologic implantation dysfunction (IID). Her husband was also evaluated clinically and had a repeat semen analysis done, along with semen cultures. The results of all these tests indicated that there were no significant problems with either partner.

Fatima was placed on a birth control pill and began receiving twice weekly injections of estradiol valerate (E2V) 4 mg along with 0.75 mg of dexamethasone daily. Within 10 days of initiating E2V therapy, the couple arrived in Las Vegas. I performed a vaginal ultrasound evaluation and determined that she had an excellent, trilaminar uterine lining that measured 10 mm in thickness, and that her blood estradiol was in the therapeutic range of 500-1000 pg/ml. At this point, we started administering intramuscular progesterone in oil (PIO) daily, and 5 days later, two CGH normal blastocysts were thawed. Both survived and were transferred to her uterus that same day.

Outcome: Fatima subsequently conceived. Her progesterone/E2V/dexamethasone therapy was continued until the 10th week of pregnancy whereupon the dexamethasone was slowly tailed off within a week thereof. A subsequent ultrasound examination performed 3 weeks later confirmed a perfectly viable twin gestation that progressed to delivery of healthy twins (2 girls) by caesarian section at 37 ½ weeks. Now, with the babies almost 2 years old and Fatima having concluded a period of successful breastfeeding, they are targeting a 2nd attempt. This time they only want a single CGH normal blastocyst transferred in order to avoid another multiple gestation.

Conclusion: IVF with egg donation is highly successful, with the vast majority of women conceiving within 2 or 3 embryo transfers. By combining this simple and effective procedure with CGH and staggered IVF (separating the cycle of egg retrieval from the cycle of embryo transfer) the efficiency, the success and convenience of the process is markedly enhanced at no additional financial cost to the patients. Finally, the fact that this process provides some assurance to patients that they are highly likely to reach embryo transfer often makes this approach much more desirable than traditional IVF.

Addendum: IVF is an ART-Science blend and not all practitioners agree on the same strategies. Thus, in the final analysis, it is important, after discussion with your personal doctor, to follow his/her advice to the letter.