By Bradford Kolb, MD, FACOG Board Certified, Reproductive Endocrinology and Infertility

Reproductive medicine has expanded treatment options to many who would otherwise not be able to have children. Despite these advances, many still experience challenges and the emotional distress of unsuccessful treatment. While some continue treatment, others succumb to these stresses and give up pursuing treatment or seek unproven therapies.

First and foremost, it is important to stress that the lack of success is not the patient’s fault. Nor does it mean that a carefully thought-out treatment plan will always be successful. Often it is in a couple’s best interest to take a step back and take a break from treatment. Taking time to “reconnect” with your partner is vital to a healthy relationship. It is also vital that your physician take a second look at your case, reviewing your records and course of treatment to date. It may be necessary to pursue further testing or to update some tests. It may be necessary to change course in your treatment or it may be determined that you are on the right track. Much of fertility is about the numbers…in other words, with continued treatment, many will find success. Even under the very best of circumstances, there is no guarantee that a treatment will result in a successful pregnancy.

For the male, an in-depth evaluation of the sperm can yield useful information. Beyond the routine semen analysis, it may be necessary to evaluate the chromosomes for evidence of environmental stresses. Excessive exposure of the testis to heat or to environmental toxins can result in fragmentation of the chromosomes, thus compromising the opportunity for a successful conception. The Sperm Chromatin Structure Assay (SCSA) evaluates the chromosomal structures for any evidence of excess stress. When abnormal results are uncovered, it is important for the male to undergo a complete evaluation, looking for any abnormal blood flow patterns to the testis or environmental exposure to toxins. Exposure to smoking and excessive heat should be avoided. Dilated blood vessels to the testis may need to be removed. When these measures are unsuccessful, there is evidence that reveals the direct extraction of the sperm from the testis may improve treatment success. The extraction of sperm, Testicular Sperm Aspiration, is a painless office procedure that is performed under anesthesia, which allows for removal of newly produced sperm before it is adversely affected by negative factors.

While your IVF cycle may yield good quality embryos, this is only a descriptive term and does not convey any information regarding the genetic normality or viability of the embryos. A number of options should be considered. First, if one’s embryos look reassuring at the cleaved stage (three days old), one may consider growing them to the blastocyst stage (five-day-old embryos). This may help identify the best and healthiest embryos to transfer. This step needs to be taken cautiously as, if the embryos are showing signs of stress early, or if there are only a few embryos, there is a risk that leaving the embryos in culture for a few extra days may adversely affect your chance of conception. There are few absolutes and it is the job of your physician and embryologist to re-evaluate your treatment each step of the way so as to maximize your chance of conception. Over the last five years, we have found that there is a subgroup of patients that benefit from the transfer of their embryos at a much earlier stage. This is done through a procedure called Zygote Intrafallopian Transfer (ZIFT). When fertilization occurs naturally, the embryos spend the first three days in the fallopian tubes prior to entering the uterus and implanting (attaching). Despite advances in embryo culture media and improved laboratory conditions, we have found a subgroup of patients whose embryos are compromised and should be transferred much earlier. ZIFT is actually an old procedure, but can significantly improve treatment outcomes when used in the appropriate couple. In a retrospective review of over 100 couples that have failed two or more standard IVF procedures, pregnancy rates were increased by 18% when an equal number of embryos were transferred directly into the fallopian tubes asopposed to the uterus. The transfer does require a normal pelvis and fallopian tubes and involves a minor surgical procedure called a laparoscopy.

Table 1

IVF ZIFT

Age 36.4 35.9

Average Number of

Failed IVF Procedures 2.3 2.1

# Oocytes Retrieved 12.4 +/- 2.3 11.0 +/- 0.9

# Embryos Transferred 3.3 +/- 0.3 4.1 +/- 0.3

%Positive hCG (p<0.01) 39.3 58.6

# of Gestational Sacs 1.1 +/- 0.3 1.6 +/- 0.6

% Ectopic Pregnancies 0 0

IVF stimulation protocols (medications utilized to stimulate egg growth) should be reviewed carefully. It is important that your physician evaluate the ratio and amount of medications utilized. There are a variety of stimulation protocols commonly utilized, but for patients that respond poorly to their medications, we have found that “estrogen priming protocols” have improved the number of eggs retrieved and the number of embryos created to transfer. Another novel technique is the use of “natural IVF protocols”. This has been found to be particularly beneficial in those who only make a few eggs regardless of the type of stimulation utilized. With this protocol, patients are not given any stimulation medications and when they develop a mature follicle, it is retrieved. The major benefit of this procedure is that it eliminates the need for stimulation medications, thus reducing the number of injections and the cost of treatment significantly, thus reducing stress significantly.

Genetic normality of the embryo is necessary for a successful conception. When appropriately evaluated, a surprising number of embryos are found to be genetically abnormal. HRC Fertility has partnered with Gene Security Network to develop a revolutionary new test to evaluate embryos. The test allows the most comprehensive genetic analysis of embryos available and may help detect factors associated with reproductive failure as well as those embryos most likely to succeed when transferred.

For some, egg donation (the use of someone else’s eggs) or surrogacy (someone else carries your pregnancy) may become necessary choices if they are to succeed, but these choices should be considered only after a thoughtful review of their case is made. The treatment options discussed above and other novel treatment plans will lead to improved treatment success and minimize the need for egg donation or surrogacy.

It is also important to consider the experience of your center and its lab. Patients need to feel comfortable with the physician and their nurses. Centers that take time to appropriately evaluate their patients, and have invested in state-of-the-art laboratories and staff, are much better positioned to help their patients. Centers with long standing labs and those that participate in original research and multicenter research studies, have the advantage of being able to access the latest technology and to apply this to their patients.