According to the latest statistics from the Society for Assisted Reproductive Technologies (www.sart.org) in the year 2011, there were a total of 154,412 cycles performed in the US. The pregnancy rates have increased compared to a few years ago, but even in young patients (< 35 y), the live birth rate remains less than 50% (46.3% per transfer). In older patients, the pregnancy rates are lower (38.4% in ages 35 – 37 y, 27.5% in ages 38 – 40 y, 16.6% in ages 41 – 42y and 6.5% in ages > 42 y). Even with egg donors, the live birth rate in 2011 was 54.9%. A relevant question would be to ask, “Why does IVF fail?” Why don’t we have a 100% pregnancy rate? Why do pregnancy rates drop in older patients? This blog will briefly try and answer these very important questions. These are also some of the issues that are part of the discussion when I meet with patients after an unsuccessful IVF cycle. Read on.
For IVF to work we need “good” egg and sperm to make “normal” embryos that will result in a pregnancy when “properly” placed in a “receptive” uterus. Let us now discuss each of these issues in detail.
Problems with egg quality (diminished ovarian reserve)
This is probably the most difficult issue we face in reproductive medicine. A woman is born with all the eggs she will have and with age, the egg quality diminishes with an increase in chromosomal abnormalities (aneuploidy). Also, women do have a “biological clock” and in some women, the egg quality will decrease prematurely (diminished ovarian reserve, DOR). We have tests to diagnose DOR and suggestions to optimize fertility. However, currently, there is no treatment for “bad” eggs. This is one of the most common reasons for IVF failure. The live birth rate for women < 35 y with a diagnosis of DOR was 36.5% in 2011 despite a high cycle cancellation rate (16.1%)! The pregnancy rate will, of course, be MUCH lower with severe egg factor.
What about the male factor?
Not much of a problem in most cases. With the advent of intracytoplasmic sperm injection (ICSI), we are able to overcome most cases of male factor infertility. We are currently routinely able to help couples where the wife makes more eggs than the husband’s sperm! Even in men with no sperm in the ejaculate, we are able to retrieve sperm from the testes (testicular sperm aspiration, TESA) and achieve pregnancy. According to SART, in 2011 the live birth rate for patients with a diagnosis of a malefactor was 48.3% in women < age 35 y. However, the pregnancy rate will be much lower when there are chromosomal abnormalities in the male (e.g. balanced translocation). A man makes a new sperm every 72 days or so. This is the reason why older men are able to father children (e.g. Charlie Chaplin, Anthony Quinn, Rod Stewart).
During IVF we generally stimulate patients with fertility drugs (gonadotropins, FSH, hMG) to produce multiple eggs. If the stimulation is sub-optimal, then it will result in poor quality eggs being retrieved. Critical aspects of stimulation include choice of medications, dose and duration. If the hCG trigger shot is given too early or too late, the egg quality will once again be compromised (immature or post mature eggs). A good quality stimulation can make a huge difference in the outcomes.
Embryo transfer technique
Embryo transfer (ET) is a critical step for an IVF cycle to succeed. For implantation to occur, the embryo(s) must be transferred without damage (traumatically) into the uterine cavity. Several improvements have occurred over the past decade, which has resulted in optimizing the ET technique. This includes the use of soft catheters, ultrasound guidance, removing the cervical mucus, avoiding instruments to grasp the cervix (tenaculum), avoiding touching the uterine fundus with the catheter tip, transferring the embryo (s) in the middle or lower third of the cavity, etc. Most good clinics will monitor individual physician ET pregnancy rates as part of an ongoing quality control routine.