Why IVF fails. ?

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).

Stimulation

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.

Implantation failure

Most IVF cycles will fail after ET. A relevant question one can ask is, “Is the body rejecting the embryos?” This used to be a hotly debated issue 15 – 20 years ago when IVF pregnancy rates were much lower. A hypothesis suggested by a small group of investigators was that implantation failure was due to the immune system rejecting the embryos. Of interest is the fact that almost 40% of infertile patients will have at least one abnormality when these immune panels were done. This resulted in a large number of patients being treated with blood thinners (Heparin, Lovenox, baby aspirin) and even expensive therapies such as intravenous gamma-globulin (IVIG).

There was a paper from a group of investigators (Denis et al.) published a paper in the late nineties that seriously questioned the validity of these tests. They ran these immune panels on approximately 700 consecutive IVF patients. The results were very interesting. There was NO correlation between the immune test results and who got pregnant, who did not get pregnant, who miscarried, and who had a baby!
The current thinking is that it is possible that the immune system has a role in implantation failure. There, however, isn’t a single test that can reliably detect these patients. At InVia, we have not recommended these tests for many years now.

To summarize, egg and embryo quality are the major reasons why IVF fails. With current technology, it is now possible to screen embryos for aneuploidy. However, there are more than 20,000 genes and currently, it is not possible to screen embryos for every genetic disease known to man. Also important are good stimulation protocols, quality control in the embryology lab, and ET technique.

Author Bio

Dr. Prakash Patel

He is a highly respected Infertility and IVF Specialist with an extensive medical career spanning over two decades. As the Director of Shukan Hospital & IVF Centre, he has dedicated his life to helping couples achieve their dreams of parenthood. He is renowned for his expertise in advanced laparoscopic surgeries and has successfully managed numerous complex cases involving recurrent miscarriages and recurrent IVF failures. His proficiency in high-risk pregnancy management and advanced IVF treatments makes him a trusted name in the field of reproductive medicine.

His approach to patient care is deeply compassionate, combining his vast clinical knowledge with a commitment to personalized treatment. He holds prestigious certifications from leading medical institutions in France and Croatia, reflecting his dedication to staying at the forefront of medical advancements. With memberships in notable organizations like FOGSI and ISAR, He is recognized both nationally and internationally for his contributions to gynecology and reproductive health.

Under his leadership, Shukan Hospital & IVF Centre has become one of the premier fertility centers in Gujarat, known for its state-of-the-art facilities and patient-centered care. His outstanding work has earned him several accolades, including the My FM Achiever Award, further cementing his reputation as a leading specialist in his field.