My IVF Treatment Failed... Now What?
An unsuccessful IVF cycle, after all the preparations it takes, is often emotionally and financially devastating. We know this well, because most of our patients come to us after having failed IVF cycles elsewhere. We also know, however, that failed IVF cycles can provide clues for a successful next IVF treatment.
Our confidence on this issue derives from the fact that we have helped so many patients over the years to conceive, despite long histories of unsuccessful fertility treatments. Indeed, many patients come to CHR after their initial fertility centers have given up on them, and refuse further treatments (unless, of course, patients agreed to donor eggs). If you are one of these patients with multiple failed IVF cycles, consider contacting CHR for a second opinion!
What is a failed IVF cycle?
"Failed IVF" is a vague term that can refer to several different situations:
- IVF cycle cancellation, prior to egg retrieval, because not enough follicles are produced;
- No or only inadequate quality eggs are retrieved;
- Retrieved eggs don't fertilize of fertilize inadequately;
- As a consequence no embryo may be available for transfer into the uterus;
- For a variety of reasons transferred embryos may not implant;
- And that, of course, will mean no pregnancy after embryo transfer.
IVF cycle cancellation
Amongst patients who come to us after cycle cancellation, a number of major problems stand out: The one most frequently encountered is that most IVF centers routinely cancel IVF cycles if the patient does not demonstrate a minimal number of follicles on ultrasound. Such cancellations make sense, if a better ovarian stimulation can be applied in a subsequent cycle. However, if a patient with diminished ovarian reserve (DOR), evidenced in part by high FSH, is already on maximal stimulation, what would be the purpose of a cycle cancellation? In such cases, nothing better can be offered in a subsequent cycle. Such a cancellation may only waste the patient's last good chance of pregnancy, because time is usually not on her side!
Often patients are not given an ovarian stimulation protocol that suits their "ovarian age." The reason for this error is that IVF stimulation protocols are usually chosen based on a patient's age. However, younger women may suffer from undiagnosed premature ovarian aging (POA): Their ovaries behave "older" than they should. Those ovaries then need to be stimulated like ovaries of an older woman, and that is very frequently overlooked. For a successful IVF treatment, patients must be given ovarian stimulation protocols based on their ovarian age, not their physiological age!
There is another worrisome trend that has developed In recent years: some centers have started to propagate so-called "mini-IVF." Proponents argue that milder ovarian stimulation is better, and results in better pregnancy chances. There is only one problem with this concept (as attractive as it may sound): None of these proponents has ever reported data that would really confirm these claims! Trying to confirm this concept, investigators, indeed, recently did a cooperative study of such "mini-IVF" and regular IVF cycles and were unable, even in young women with entirely normal ovarian reserve, to demonstrate either clinical or economic benefits of "mini-IVF." Very much to the contrary! "Mini-IVF" produced lower pregnancy rates and showed no cost advantages.
Yet, "mini-IVF" is widely propagated for women with much poorer prognosis - women with DOR - and they can be expected to do even worse than the young, normal women investigated in this CHR study. With mild ovarian stimulation, DOR patients face an approximately 50% cycle cancellation rate, unheard of in any responsible IVF format!
At CHR, our approach is different. We are not afraid to use more aggressive forms of ovarian stimulation, if test results and thorough examinations of the patients show that low ovarian reserve requires such treatment. By careful monitoring during ovarian stimulation, most negative side effects of stronger ovarian stimulations can be avoided. This is exactly what our physicians and nurse coordinators do.
CHR's basic philosophy is to "fight for every single egg." Therefore, we will go after even a single egg in some patients, if a patient manages to produce one follicle. While pregnancy chances are obviously small with retrieval of only one egg (and the risk of not retrieving an egg from a single follicle is considerable), it takes only one egg and one embryo to establish pregnancy. Many CHR patients can confirm this fact: their voices are heard on our success stories page!
Differences in CHR philosophy derive from the fact that CHR patients are different from patients at practically all other IVF centers. Having very few eggs is "normal" at CHR. A large majority of our patients come to our center because they already know, from prior IVF experiences elsewhere, that they produce only very small numbers of eggs, and that they need a fertility center that will fight for those few remaining eggs.
With the help of dehydroepinadrosterone (DHEA) and our individualized ovarian stimulation protocols, we have learned to get the most out of these patients' ovaries. Most patients who come to CHR after previous experiences will tell you that they, at CHR, end up with more eggs and embryos, and they are of better quality. Every egg and embryo counts, because every egg and embryo represents pregnancy chances!
Poor quality eggs and poor quality embryos
CHR Publications on DHEA
- Human Reproduction The article demonstrated that even with extremely low serum AMH levels (below 0.1 - 0.4 ng/ml), moderate but reasonable live birth chances can be expected with DHEA supplementation and proper ovarian stimulation. 70 women younger than 42 years had a 14.3% live birth rate after IVF, while 58 women over 42 had 3.4% live birth rate.
Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR).Journal of Assisted Reproduction and Genetics The lastest CHR study of DHEA and female fertility, the study found that androgen conversion rates after DHEA supplementation vary depending on women's age and FMR1 genotypes. Younger women converted DHEA into testosterone much more efficiently than older women. Benefits of DHEA supplementation on IVF pregnancy rates were predicated on efficiency of androgen conversion.
An IVF cycle can be unsuccessful even with good numbers of eggs (and embryos) if egg quality is poor. Egg quality reflects about 95% of the final quality of an embryo. Poor egg quality, therefore, always leads to poor embryo quality. The quality of sperm, while not unimportant, is minuscule in comparison to egg quality.
Embryos from low-quality eggs often fail to develop properly. In an IVF cycle, embryos are observed for 3 to 5 days as they grow, before they are transferred into the uterus. On the third day, good-quality embryos should reach 6- to 8-cell stage, and have a more or less regular shape. Embryos that don't reach this stage within the first few days of development cannot be used for embryo transfer. In addition, some embryos that do reach this stage may be aneuploid (have chromosomal abnormalities). Aneuploid embryos, if they implant at all, are usually miscarried early in the pregnancy, thus also resulting in "failed" IVF.
Therefore, as many of our patients already know, it is not just the number of eggs that is important. The quality of eggs is also crucial for the success of IVF. In this context, our development of dehydroepiandrosterone (DHEA) in women with DOR becomes important. Our initial finding was simply that DHEA supplementation increases the IVF pregnancy rates, especially in women with diminished ovarian reserve (DOR). However, over the years, we have also confirmed that DHEA supplementation improves egg quality, improves embryo quality, and reduces aneuploidy (chromosomal abnormalities) in embryos.
By using DHEA along with a well-designed IVF protocol for each patient, CHR physicians have been able to achieve once unthinkable results: women with a long history of failed IVF cycles and/or very low ovarian reserve are conceiving in significant numbers! Please contact us to see if whether our DHEA protocol may be of help to you.
Conditions that can prevent embryo transfer
IVF cancellations can also happen when the patient develops medical complications that make it impossible to transfer embryos to her uterus. Two such conditions are ovarian hyperstimulation syndrome (OHSS) and inadequate endometrium.
OHSS is a rare side effect of ovarian stimulation. In most cases, OHSS remains mild and only cause minor to moderate discomfort. However, in women with DOR, OHSS is exceedingly rare, and rarely of concern. When OHSS is more severe, however, embryo transfer may need to be cancelled, and all embryo are frozen for future use. Significant OHSS is usually, though not always, preventable with proper monitoring and adjustments in fertility drugs during ovarian stimulation. Women with polycystic ovaries are generally at highest risk.
The other condition, inadequate endometrium, is also rare but can be a frustrating challenge. Most IVF patients develop good enough endometrium (lining of the uterus) to receive their embryos. When a patient's endometrium is slow to develop, various medications can be used to help encourage the proliferation of the endometrium. These conventional medications are enough for a majority of IVF patients, and these patients have their eggs retrieved and embryos transferred.
In a small number of IVF patients, however, endometrium can stay unresponsive to conventional treatments. Since a thickness of 7 mm is considered minimal for a decent chance of embryos implanting, inadequately thin endometrium can be a reason for cancellation of IVF cycles. When embryos are transferred despite inadequate endometrium, the transfer usually result in implantation failure.
CHR recently reported in Fertility & Sterility a new treatment for women with endometrium resistant to standard treatments. Because this was just a small case series, we are currently conducting a clinical trial of the drug we used in these few patients successfully to determine if it, indeed, improves the endometrium in patients, otherwise persistently unresponsive. If you have experienced implantation failure, you may benefit from participating in the trial. Please contact us to see if you qualify.
Unexplained IVF failures – Possible autoimmune involvement
Perhaps the most frustrating of IVF failures may be the ones for which no apparent reason can be found. A factor, often overlooked in investigation, is the female's autoimmunity (immunity against oneself).
Female autoimmunity's impact on reproduction has been contentious among IVF experts, but published evidence suggests that even subclinical autoimmunity (autoimmunity that doesn't require medical treatment and is not obviously apparent) can negatively impacts fertility. Norbert Gleicher, MD, Medical Director of CHR and an internationally renowned expert of autoimmunity in reproduction, emphasizes that when repeat IVF failures cycles appear to have no cause, autoimmunity should always be investigated. At CHR, patients with evidence of autoimmunity then receive a treatment to keep their autoimmunity in check. This has resulted in many successful IVF births in women with previous autoimmune-related IVF failures.
In 2010 CHR investigator were able to demonstrate a genetic marker for autoimmunity, which, likely, reduces the pregnancy chance with IVF to a significant degree. This paper appeared in the prestigious electronic medical journal PLoS ONE. Autoimmunity, indeed, appears much more important in infertility than is widely appreciated. Should you believe that you might have an autoimmune problem, please contact us!
What to do when IVF cycles fail
Even when every step—from ovarian stimulation to egg retrieval to embryo transfer—goes as planned, the reality is that a certain percentage of women will not see a positive pregnancy test. IVF pregnancy rates, overall, have improved tremendously in the three decades since the technique was initially introduced; but it still is not perfect. Especially among women with DOR (either due to natural age or due to premature ovarian aging), negative pregnancy tests are unfortunately still common, and patients who still want to work with their own eggs have to expect that it may take more than one cycle to conceive.
Dr. Norbert Gleicher explains CHR's extensive experience in treating "tough" infertility cases.
The important question is whether we can improve upon unsuccessful cycles. At CHR we learn from every unsuccessful cycle. Every IVF cycle that did not lead to pregnancy is discussed and dissected in our weekly conference. This is the only way to get better. And getting constantly better is at the core of CHR's existence. As a fertility center that has been pushing the boundaries of fertility treatment for the past three decades, CHR has treatment options that other centers cannot offer.
To see whether CHR can help you after you have failed IVF elsewhere, please contact us.
CHR is an expert resource on finding ways to make IVF successful. Please contact us if you have any questions or would like to know more about our treatments.
Written by David Barad, MD
Last Updated: November 21, 2013