The same is true for the most time consuming and expensive treatment protocols involving IVF. The IVF process begins, in most cases, with a downregulation period whereby natural secretion of endogenous hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH), is suppressed (down regulated) prior to initiation of injections of fertility medications. This is often achieved using daily injections of a medication called Lupron®. Once down regulation is confirmed, by a blood test and an ultrasound examination, daily injections of fertility medications (Repronex®, Gonal-F®, or Follistim®) is begun, often lasting eight to nine days. The purpose of administering such medications is to stimulate the ovaries to produce multiple follicles (in a natural cycle a single follicle is commonly selected for growth and ovulation), so that multiple eggs harbored in such follicles can be harvested.The ultrasound examinations are performed regularly along with blood tests, every two to three days during the stimulation period, to follow the development of follicles within the ovaries. Once several of the follicles have reached a mature size, ovulation is induced with yet another injection, human chorionic gonadotropin (hCG). Next, eggs are recovered from the ovaries 36 hours later in a minor surgical procedure called transvaginal ultrasound-guided follicle aspiration. Mature eggs are mixed or injected with sperm (intracytoplasmic sperm injection, ICSI) in a small dish in the laboratory and fertilization of eggs is assessed the next morning. If fertilization had occurred (successful approximately 80% of the time), the development of the now growing embryo (early fetus) is followed daily until the third day of the embryo's life (three days after egg retrieval). Meanwhile, the patient injects herself daily with progesterone shots in preparation for the embryo transfer procedure. Next, three day old embryos of the highest quality are transferred into the patient's uterus using a special catheter inserted through the patient's cervix. A pregnancy test is performed 9 to 11 days later. Now, imagine failing this process one time. Imagine failing this process two times. Imagine failing this entire process three times or more. Devastating? Absolutely! Couples who have failed IVF multiple times are often depressed, angry, disappointed, discouraged, and in general emotionally, physically, and financially drained. If IVF, the procedure with the highest success rate for achieving pregnancy, has failed, what other hope is there? When standard IVF and trans-cervical embryo transfer have failed multiple times, common practice among fertility specialists has been to offer couples a procedure in which gametes (eggs and sperm) or zygotes (day-one embryos) are transferred into the fallopian tubes instead: gamete intra-fallopian transfer (GIFT), or zygote intra-fallopian transfer (ZIFT). Several studies have shown significantly higher success rates with GIFT or ZIFT as compared to standard IVF. In GIFT and ZIFT, all steps from downregulation to ovarian stimulation to egg retrieval, are identical to standard IVF. However, several important differences exist. In a GIFT procedure, retrieved eggs and sperm are mixed together and transferred into one or both fallopian tubes (where natural fertilization normally occurs). In a ZIFT procedure, on the other hand, fertilization is allowed to take place in the laboratory just like in standard IVF, however when day-one embryos are formed, they are transferred into the fallopian tube(s) instead of the usual transfer of day-three embryos into the uterus through the cervix, as in standard IVF. The transfer of gametes, or early embryos, into the fallopian tubes requires a surgical procedure called a laparoscopy. Several limitations exist with either a GIFT or ZIFT procedure. First, tubal embryo transfer is not suitable for patients with tubal factor infertility, as at least one normal tube has to be present. Second, not all fertility programs can offer this procedure since it requires surgical intervention at the time of, or one day following, the egg retrieval procedure. This requires that a laboratory equipped to handle gametes and embryos be in close proximity to an operating room. Third, success rates, although reported to be higher than standard IVF when prior IVF cycles have failed, are only modestly higher and are individualized to different IVF clinics. In our program, for example, we found that with prior failed IVF cycles, a GIFT or ZIFT procedure achieved similar pregnancy success rates to standard IVF, however were more expensive and potentially risky. So what is next? Recently, yet another technique had been described offering the infertile couple who had exhausted all other standard treatment modalities (IVF, GIFT, ZIFT) true hope: combination GIFT/IVF or ZIFT/IVF. In these procedures, all known technologies are combined to maximize success rates. After transfer of gametes or day-one embryos into the fallopian tube(s) via laparoscopic surgery (a GIFT or ZIFT procedure), remaining embryos that had been left to develop in the laboratory are transferred into the uterus through the cervix two or three days later, when the embryo is three days old. The advantage of combined treatment is only one: highest pregnancy success rates in couples who have failed multiple prior cycles of standard IVF. In a recent review of over 100 of our own cycles of combined GIFT/IVF and ZIFT/IVF procedures, couples that had failed on the average at least 2 prior IVF cycles had a clinical pregnancy rate of 60% across all age groups, the oldest patient conceiving at age 44 (data soon to be published). Twin and triplet pregnancy rates were found to be identical to standard IVF, reassuring that transfer of more gametes or embryos in the combined procedure did not result in any significant increase in the multiple gestation rates, compared to IVF. Inability
to conceive can be a devastating phenomenon to a couple.
Often times, the road of fertility treatment may be
torturous and full of disappointment. Thanks to medical
advances in the field of Reproductive Endocrinology
and Infertility, couples that had met previous failure
can now be offered new procedures that may significantly
enhance success rates and offer renewed hope.
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