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It’s all in the Details…And it’s all details!

The recently published article by Luke et al in the New England Journal of Medicine (Cumulative birth rates with linked assisted reproductive technology cycles  NEJM 2012:366;26) might seem to confirm this mistaken belief if not read with caution.  The problem with the assumption that trying continuously will result in a success is in the word “infertility.”  Infertility is variably defined as not conceiving after one year of attempting to conceive.  It lumps all people failing to conceive after a year of trying into one basket. The underlying principle is that if a person does not conceive within a certain then there may be a problem that could be solved with medical intervention.   Time for the details!  Some people will conceive with or without any intervention. Some people can be helped with medical intervention. Unfortunately, some people are sterile and will not succeed no matter how frequently or extensively they use medical intervention.  The problem, of the ‘details’ is how to define into which category a person falls. This is where using a diagnosis and statistics can help a person decide which therapies to use and for how long. Knowing both the diagnosis and the success for a given therapy, allows a person to compare the treatment success rate to the treatment independent success rate and establish when treatment is successful and when it becomes no better than not doing anything.

The study in the NEJM does not compare success rates with medical treatment to success rates without medical treatment since accurate data on spontaneous pregnancy rates for infertility couples were not available in this study.  Spontaneous pregnancy rates for couples who stop treatment after IVF have been estimated to be anywhere from 2-25% with advanced age being associated with the lower success rates.  That means that a woman at age 41 who does not conceive with IVF after more than one attempt may not be increasing her chance of having child by continuing to use her own eggs, with or without medical treatment.  Her expectation for conceding without doing anything is also extremely low.  A gambler would refer to this as chasing your losses.  But, would the knowledge about her high chance of success using donor eggs as reported in this study help sway her decision?

The strength of the study by Luke et al is the size of the data base they evaluated. It was derived from the national data reporting system for SART in the US and included information from 471,208 cycles of IVF.  The study was designed to calculate the overall chance of having a child if IVF was used more than once.  Many times the success rate for IVF is expressed as the chance of delivery per cycle. But what would be the chance of success for the second, third… or twentieth cycle?  The statistic used to determine this is the cumulative pregnancy rate which is the percentage of patients doing two or more cycles who actually have a child. This approach can be both helpful and misleading. For example, suppose a 35 year old female with a diagnosis of male factor and unlimited funds wants to know what her chance of having child would be if she chooses to do IVF up to six times. The study gives both an optimistic and a conservative estimate which estimates her overall chance of success (over six cycles) between 60 and 85%. Suppose now this woman has done five cycles of IVF but is not pregnant. Does that mean with her sixth cycle of IVDF she has a 60-85% chance of having a child? Absolutely not!  In fact on her sixth cycle of IVF she may actual have less than a 3-5% chance of success. The value of the cumulative pregnancy rate is to help a person decide how they want to structure their overall treatment plan from the beginning.  But, review must be done along the way as well!  So, for the patient facing her sixth cycle of IVF using her own eggs and a 3-5% chance of success, she may decide to use donor eggs since they would afford her a far greater chance of success.

Therefore, the knowledge about her high chance of success using donor eggs as an option, in addition to the cumulative pregnancy rates as reported in this study can be very helpful in making a decision, at any point in the process.

Playing to Win

The conclusions from this study were:

  1. The use of both a person’s own oocytes plus the use of donor eggs as an alternative resulted in pregnancy rates that were comparable to natural pregnancy rates for people without infertility.
  2. The overall chance of conceiving was age related. Older women had a lower chance of success if they only used their own eggs. If they were will to use their own eggs and if that failed they war willing to use donor eggs, then they had the same chance of having a child as younger women.
  3. Patients with reduced ovarian reserve or with uterine factors had a lower overall chance of success even if they were younger. Thus a young woman with a reduced ovarian reserve may wish to use donor eggs sooner than another young woman with a diagnosis of male factor. Or a woman at any age with a uterine factor may wish to consider a gestational host sooner than a woman without a uterine factor if she is unsuccessful using IVF and her own uterus.

The overall summary is that IVF does work, and if all options are utilized by a person, the chance for having a child is extremely high.

Contrary to this, when continuing down the same path in the face of grim statistics and multiple failures, it may also be helpful to refer to the (nonscientific) adage of the definition of Insanity…Doing the same thing over and over and expecting different results!

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