The objective with In Vitro Fertilization is to consistently transfer competent embryos into a receptive uterine environment. This requires a very individualized and meticulous approach to evaluating and addressing those factors that can influence IVF outcome: All patients/couples should learn what they can reasonably expect before committing to IVF. And finally, is important for patients/couples to have realistic expectations and to “plan the trip” before embarking on the IVF journey
While it is true that it will often take more than one IVF attempt to achieve a successful outcome, it is not good enough to simply advance this argument as a reason to just “keep on trying. Ninety percent of my personal IVF practice involves treating patients who have experienced two or more prior IVF failures. Some had undergone more than 10 failures and believe it or not, in one case the couple had failed more than twenty prior attempts. A common thread that often underlying such heartbreaks is the failure to thoroughly plan the IVF journey before embarking on it. Preparing for IVF requires a very individualized approach. It is important to understand that each patient/couple is different and that a “one size fits all, ‘recipe approach is inappropriate.
- Evaluation of medical suitability for IVF: The Hippocratic doctrine says “do no harm”. This means that every patient /couple must be carefully assessed medically and psychologically in advance of undergoing IVF in order to identify potential health hazards that could be revealed in the course of a cycle of treatment or during an ensuing pregnancy. For example: a) very young women, and those that don’t menstruate or ovulate regularly on their own are at inordinate risk of developing life endangering complications associated with severe ovarian hyperstimulation syndrome (OHSS) following administration of fertility drugs and require modified treatment regimes, b) women with certain hereditary blood clotting disorders ( thrombophilia) are at much greater risk of early and late pregnancy complications and require specific treatments as soon as pregnancy is diagnosed, c) Women with cardiovascular disease or hypertension are at greater risk of developing pregnancy related complications that can compromise their well being as well as that of their baby(ies) d) Some women have hidden bleeding disorders due to blood platelet disorders or abnormalities in certain blood clotting defects which if undiagnosed can lead to serious complications during egg retrieval, e) The presence of active viral and bacterial sexually transmittable diseases should be identified and if possible treated in advance. In some cases where the risk of transmission to partner of baby cannot be avoided, detailed advance disclosure and counseling is essential. These are but a few examples to illustrate the point .There are many, others.
- Defining the cause of the infertility: About one third of infertility is due to female causes, one third due to male sperm dysfunction and the remaining third is due to a combination of both male and female factors. In addition, there is very often more than a single female (or male) factor contributing to the problem. To ignore this reality, can be perilous. Here are a few examples: a) one third of women who have endometriosis also have a concomitant immunologic implantation problem. In such cases, the performance of IVF without appropriate selective immunotherapy will usually lead to failure; b) Tubal damage necessitating IVF is sometimes associated with internal uterine scarring and a poor endometrial thickening. By-passing the tubal issue through IVF will usually not achieve a viable pregnancy unless the uterine lining can be improved concomitantly.
- Timing of treatment: With a few exceptions, women who have very diminished ovarian reserve (DOR) and accordingly are usually poor responders to fertility drugs, and require repeated IVF attempts need at least one full resting cycle before undergoing a repeat attempt.
- Selecting the ideal protocol for ovarian stimulation: Most IVF failure to is attributable to “poor embryo quality.” In many cases, irreversible factors such as advanced maternal age or severe and often intractable male infertility often are at the root of this problem. However, poor embryo quality mostly stems from poor egg quality which in turn is it is due to poor egg development in advance of administering the hCG trigger. This boils down to the selection of suboptimal protocols for ovarian stimulation and inappropriate timing of the administration of the hCG “trigger.
- Resorting to Staggered IVF with Embryo banking and preimplantation genetic testing (PGT) to try and offset the biological clock: The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”. While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGT (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
- Moving to third party parenting: There comes a time when it is necessary to decide whether to solicit the assistance of an egg donor or a gestational surrogate or whether to stop trying. Menopausal and premenopausal women of any age and women over 43 (for whom the chance of successful IVF using own eggs is very small) should be advised to move to egg donation. Women with serious health hazards that contraindicate pregnancy and those who do not have functional uteri or who have an intractable immunologic or anatomical implantation dysfunction should consider using a gestational carrier. Likewise, there should be a timely recommendation for sperm donation made to men who have incurable absence of sperm production and those with intractable severe sperm dysfunction.