Natural IVF Treatment Options
There are two basic patient groups for Natural IVF Protocols, those patients that should respond well to stimulation and those that do not. The Center for Natural IVF employs varying protocols to address the uniqueness of each patient's known or expected response to treatment.
In order to help you better understand the relative advantages and disadvantages of all of the variations of the no stimulation and low dose protocols, we have summarized below a number of important references. Your doctor can help you interpret these protocols and determine which might fit your needs the best.
Truly Natural IVF
Truly Natural IVF implies the complete absence of drugs. In a normal menstrual cycle, a single follicle containing a single egg develops. This approach relies on the monitoring of the development of this follicle and the proper timing of its retrieval from the ovary.
The process for a true natural IVF cycle involves close monitoring of the woman's follicles starting cycle day 9, and twice daily urine LH testing that will be done at home. When the follicle(s) have matured, and an LH surge has been reached, the patient will be brought into the Center for egg retrieval. The eggs will be fertilized through conventional methods, or the use of ICSI may be necessary in some cases.
In vitro maturation (IVM)
IVM is an emerging technology that is relatively new to the field of human fertility treatment. The underlying tenet of IVM is that, during the natural course of a woman's menstrual cycle, immature eggs are retrieved from the ovaries and are matured in the laboratory for several days. The eggs that reach maturity in vitro, are then fertilized with sperm and allowed to develop into embryos over the subsequent three to six days. Because the eggs are being retrieved at an immature developmental stage, there is no need for standard stimulation medications.
Women undergoing IVM have a much lower implantation rate when compared to a traditional, stimulated cycle. However, the IVM cycle may be appropriate for certain cohorts of women facing confounding medical issues associated with a stimulated cycle. Women for whom IVM would be particularly useful are those with polycystic ovarian syndrome (PCOS), women who have developed ovarian hyperstimulation syndrome (OHSS) in a previous traditional IVF cycle, or women wishing to limit their exposure to very high levels of circulating hormones (e.g. patients with a hormone-sensitive tumor). An additional advantage to IVM is that the egg retrieval can be scheduled for a particular day well in advance of the cycle.
The IVM process includes taking estradiol orally three times daily. An ultrasound will be performed on cycle day 12-14 to assess the endometrial and follicular response to the estradiol. Depending on the progress of the endometrium and follicles, an oocyte retrieval will be scheduled between cycle days 16 and 20. Once the immature eggs are retrieved, they will be matured in vitro for up to 72 hours following the retrieval. In most cases, intracytoplasmic sperm injection will be used to ensure proper fertilization of the eggs. Those eggs that do fertilize will be cultured for up to 5 days to ensure the best chance for implementation.
Natural IVF with HCG trigger
Without the use of medications, it is difficult to predict the timing of the maturation of the dominant follicle, and thus the egg retrieval. The bioidentical hormone HCG acts just like LH (luteinizing hormone), the pituitary hormone that stimulates egg maturation and release. HCG therefore facilitates the timing of egg retrieval, decreasing the risk of missing the retrieval time seen with drug-free IVF. In some cases, a GnRH agonist like Synarel® or Lupron® is used instead of HCG to stimulate the pituitary to release its own LH and accomplish the same result.
The HCG Trigger protocol utilizes ultrasound and estradiol monitoring, along with twice daily urine LH testing at home. Your physician will also prescribe one dose of HCG when the follicle(s) reach an appropriate size. The oocyte retrieval will be scheduled approximately 36 hours following the HCG administration. Similar to other natural IVF protocols, intracytoplasmic sperm injection (ICSI) will likely be used to ensure fertilization of the eggs.
As with drug-free IVF, a high cancellation rate is expected due to possible abnormal follicular development and the inability to prevent a spontaneous LH surge.
Modified natural cycle IVF
As you can see from the previously described "natural" protocols, cycle loss can be very high. To minimize cycles lost to unpredictable LH surges, a GnRH antagonist can be added to the medication regime. Since the antagonist (Ganirelix®, Cetrotide®, or Synarel®) lowers the pituitary production of FSH as well as LH, a small dose of FSH is added to promote the continuing development of the dominant follicle(s).
This protocol utilizes ultrasound and estradiol monitoring and twice daily urine LH testing at home, until the antagonist is added. When the ultrasound indicates that a leading follicle reaches an ideal size, the GnRH antagonist will be administered along with FSH each day. Finally when the ultrasound indicates that the leading follicle has reached its ideal size indicating maturity, HCG will be administered subcutaneously. Then approximately 36 hours later the oocyte retrieval will be scheduled. As in other "natural" protocols to ensure optimal fertilization, intracytoplasmic sperm injection (ICSI) will likely be recommended. Finally your physician will prescribe progesterone to support the hormone levels following the embryo transfer.
Low-Dose Follicular Clomiphene
To increase the chance of retrieving one or more eggs per cycle, while avoiding the higher cost of conventional IVF and decreasing the risk of ovarian hyperstimulation, low stimulation protocols were devised as a "middle of the road" compromise. The first of these, popularized in Asia, involves continuous clomiphene with superimposed intermittent gonadotropin supplementation.
Although this particular protocol attempts to increase the chances of successfully maturing and retrieving more than one oocyte, it does have its drawbacks. Since clomiphene is a drug that effectively blocks estrogen receptors, the lining of the uterus (endometrium) is often quite thin and unfavorable for implantation. Without a properly prepared endometrial lining, implementation will not be possible. Therefore, with this protocol, all embryos are frozen. At a later date, your physician will then schedule a frozen embryo transfer during a spontaneous cycle or estrogen prime cycle, which is especially good for creating a good endometrial environment for embryo implantation and growth.
The patient undergoing this protocol will need to take daily Clomiphene, and begin FSH injections starting on cycle day 8. Follicular ultrasounds and estradiol levels will be performed early in the cycle then again routinely starting on cycle day 10. Once the leading follicle reaches an optimal size, HCG will be injected, and the egg retrieval will be scheduled approximately 36 hours thereafter. Once the oocytes are retrieved, they will be fertilized and cultured in vitro for 3 to 6 days. Then all embryos that reach maturity will be Cryopreserved (frozen).
This process will need to be repeated for a total of three (3) cycles to ensure enough embryos can be successfully transferred and implanted. Your physician will schedule a frozen embryo transfer following a natural or artificially stimulated cycle.
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