My son is starting his second year residency in obstetrics and gynecology. He, like I was 30 years ago, is turned on by reproductive medicine and enjoys performing gynecologic surgery. When I decided then to specialize in reproductive endocrinology and infertility (REI) I was looking forward to being on the frontier of fertility medicine. The details of Reproductive physiology were being unraveled in real time and IVF had just reported its first successful pregnancies. In those days, microsurgery of the fallopian tubes was commonly performed by REIs as well as endometriosis and fibroid surgery.

During my fellowship, surgery was a huge part of my training. I travelled to Nashville to train with one of the world’s experts in laser laparoscopy. I practiced my tubal microsurgery skills weekly on anesthetized rats in a plastic surgical lab. I assisted on reproductive surgery several cases every week throughout my fellowship.

Myself and other fellows performed research on basic reproductive physiology questions that had yet to be worked out. Personally, my interest was polycystic ovarian disease and its relationship to weight gain. I studied male hormone production in the ovary and the adrenal gland before and after significant weight loss. I discovered that there was an inverse relationship between weight loss and male hormone production and that this was mediated through insulin. These were exciting times. If only we had metformin back then, I would have proven that in addition to weight loss, we could decrease insulin levels and therefore male hormone levels with metformin.

Today, discoveries in reproductive physiology are much more esoteric than it was when I was a fellow. Reproductive surgery, in particular tubal microsurgery and laser laparoscopy for endometriosis and adhesions is usually replaced with in vitro fertilization (IVF) which has become so much more successful, less invasive and therefore a preferable option. Most causes of infertility, if they are not successfully treated with ovulation induction and intrauterine insemination (IUI) can be overcome with IVF.

In the 1980’s when I was a fellow, IVF was grossly inefficient and we had to transfer multiple embryos to achieve a pregnancy. Consequently, triplets and quadruplets were not rare occurrences. In many programs, they constituted over 10% of all pregnancies. Today, we can often transfer one embryo at a time minimizing the risk of multiple pregnancies. We can freeze excess embryos so many patients need go through only one stimulation and retrieval and still have multiple transfers providing them with an excellent chance of conceiving a baby from their efforts.

Today, we get excited about advances in preembryo genetic screening and diagnosis and contemplate the current and future potential of eliminating hereditary medical disorders. This involves highly trained laboratory personnel who perform the latest technologic advances. In 2010, the REI, in general is removed from a hands on involvement with the frontiers of Reproductive Medicine and instead works like a film producer gathering his team including these lab personnel, nurses, etc and directing them as to how to approach his patients’ fertility problems. It used to be that he used the microscope and laser laparoscope to perform the tubal and endometriosis surgery. The IVF retrieval and transfer were new procedures that were still being perfected.

Today, they are the routine cases performed daily by the REI.

My son looks at the REI of today as a doctor who starts his day with 1-2 hours of ultrasound that is part of the daily ovulation monitoring for IUI and IVF. Many REIs no longer perform more surgery than hysteroscopy and occasional laparoscopy or myomectomy in addition to their retrievals. These are all considered routine procedures now. The current frontier in infertility is limited pretty much to the laboratory. Though many of us consider ourselves expert in stimulations, retrievals and transfers and while we know we make a significant difference in our patients’ outcomes our work does not appear or feel as glamorous as it once did. Perhaps, he will decide, as I did, that the pleasure in helping women build their families is sufficient reward. Or perhaps, this Nintendo generation, will seek a more apparently exciting lifestyle. How about that Robotic surgery?

Success varies with many factors. The age of the woman is the most important factor, when women are using their own eggs. Success rates decline as women age, and success rates drop off even more dramatically after about age 37. Part of this decline is due to a lower chance of getting pregnant from ART, and part is due to a higher risk of miscarriage with increasing age, especially over age 40. There is, however, no evidence that the risk of birth defects or chromosome abnormalities (such as Down’s syndrome) is any different with ART than with natural conception.

Success rates vary with the number of embryos transferred. However, transferring more embryos at one time not only increases the chance of success with that transfer, but will also increase the risk of a multiple pregnancy, which are much more complicated than a singleton pregnancy. The impact of the number of embryos that are transferred on success rates also varies with the age of the woman.

Pregnancy complications, such as premature birth and low birth weight, tend to be higher with ART pregnancies, primarily because of the much higher rate of multiple pregnancies. Nationally, in 2002-2003 about 30% of ART deliveries were twin deliveries, versus 1-2% of spontaneous pregnancies. The risk of pregnancy containing triplets or more was 6% in 2003.

As women get older, the likelihood of a successful response to ovarian stimulation and progression to egg retrieval decreases. These cycles in older women that have progressed to egg retrieval are also slightly less likely to reach transfer.  The percentage of cycles that progress from transfer to pregnancy significantly decreases as women get older.  As women get older, cycles that have progressed to pregnancy are less likely to result in a live birth because the risk for miscarriage is greater.  This age related decrease in success accelerates after age 35 and even more so after age 40.  Overall, 37% of cycles started in 2003 among women younger than 35 resulted in live births. This percentage decreased to 30% among women 35–37 years of age, 20% among women 38–40, 11% among women 41–42, and 4% among women older than 42.  The proportion of cycles that resulted in singleton live births is even lower for each age group.

The success rates vary in different programs in part because of quality, skill and experience but also based on the above factors of age, number of embryos transferred and patient population.  Patients may also differ by diagnosis and intrinsic fertility which may relate to the number of eggs a patient may be able to stimulate reflected by baseline FSH and antral follicle count as well as the genetics of their gametes.  These differences make it impossible to compare programs.

Another factor often overlooked when considering one’s odds of conceiving and having a healthy baby from an IVF procedure is the success with cryopreserved embryos.

Thus, a program which may have a lower success rate with a fresh transfer but much higher success with a frozen embryo transfer will result in a better chance of conceiving with only a single IVF stimulation and retrieval.  Success with frozen embryos transferred in a subsequent cycle also allows the program to transfer fewer embryos in the fresh cycle minimizing the risk of a riskier multiple pregnancy.  It may be more revealing to examine a program’s success with a combination of the fresh embryo transfer and frozen embryo transfers resulting from a single IVF stimulation and transfer.  For example, at East Coast Fertility, the combined number of fresh and frozen embryo transfers that resulted in pregnancies from January 1, 2005 to April 2006 was.  The number of retrieval during that time was.  The success rate combining the fresh and frozen pregnancies divided by the number of retrievals was 77.2%.  The high frozen embryo transfer pregnancy rate allowed us to transfer fewer embryos so that there were 0 triplets from fresh transfers during this time.

What can I do to increase my odds?

Patients often ask if there are any additional procedures we can do in the lab that may improve the odds of conception.  Assisted hatching is the oldest and most commonly added procedure aimed at improving an embryo’s ability to implant.  Embryos must break out or hatch from their shell that has enclosed them since fertilization prior to implanting into the uterine lining.  This can be performed mechanically, chemically and most recently by utilizing a laser microscopically aimed at the zona pellucidum, the shell surrounding the embryo.  Assisted hatching appears to benefit patients who are older than 38 years of age and those with thick zonae.

Recently a protein additive called “Embryo glue” was shown to improve implantation rates in some patients whose embryos were transferred in media containing “Embryo glue”.  Time will tell if the adhesive effect of this supplement is truly increasing success rates and warrants wide scale use in IVF programs.

Embryo co culture is the growth of developing embryos is the same Petri dish as another cell line.  Programs utilize either the woman’s endometrial cells obtained from a previous endometrial biopsy or granulosa cells obtained at the time of the egg retrieval from the same follicles aspirated as the eggs.  Growth factors produced by these endometrial and granulosa cell lines diffuse to the developing embryo and are thought to aid in the growth and development of the embryo.  It appears to help patients who have had previous IVF failures and poor embryo development.