Male Factor: Sperm Quality and Diet

A healthy pregnancy requires at least one healthy egg to be present in the company of at least one (but usually millions) of healthy sperm.  A semen analysis is usually the screening test used to check for evidence of “male factor” infertility, i.e. some deficiency in the quantity or quality of sperm that may be contributing to a couple’s difficulty conceiving. In at least 30-40% of couples undergoing evaluation for infertility, a semen analysis will reveal some abnormality in at least one of the major categories by which we judge sperm: concentration (how many), motility (what percentage of the sperm are swimming properly), and morphology (what percentage of the sperm have a normal shape).

The task of deciding whether or not the semen analysis is “normal” may seem simple, but in reality it is often hardly clear-cut. For one thing, a man’s sperm parameters can change on a daily basis, so  one borderline normal or abnormal result  may not tell the whole story. For this reason, a fertility specialist will sometimes request the male partner to produce a second sample before deciding whether or not a man has a meaningful abnormality. Many specialists will recommend a 6-10 week waiting period before repeating the semen analysis. This is because the “life cycle” of a man’s sperm is approximately 60-80 days, such that two abnormal semen analyses spaced by this much time provides stronger evidence of a “true” (i.e. persistent, as opposed to transient) problem.

While severe male factor infertility is uncommon and is usually caused by an identifiable/specific medical condition (e.g. genetic, hormonal, anatomic, etc.), more mild sperm issues are quite common and often have no specific explanation. In fact, in men with more minor abnormalities, it can be unclear as to whether the semen analysis represents a real explanation for infertility at all, as the boundaries between normal and abnormal are chosen using math and statistics, but they change over time and don’t correspond specifically to any biological process or condition (the World Health Organization reference values are the ones most commonly used; they last underwent a major update in 2010).

The lack of an explanation/reason for the problem can be frustrating for couples with mild male factor infertility. Only a few lifestyle issues have been clearly shown to be important, such as smoking, marijuana use, and steroid use. A couple of recent studies have tried to find a relationship between a man’s diet and his semen analysis. In one study, a relatively weak association was found between high total dietary fat intake and low sperm concentration and motility; this relationship was driven in large part by saturated fat in particular. In another study, men consuming an overall healthier diet had very slightly better sperm motility, but no difference in concentration or morphology.

Like many studies looking at dietary issues, these studies used diet questionnaires, which are notoriously unreliable. Furthermore, the associations the studies found were slight and their true significance is questionable. While both studies suggested the possibility of an association between a healthier diet and better sperm counts, the role of diet and nutrition in male factor infertility is far from certain and needs further, and more rigorous, investigation.

References:

1. Attaman et al. Human Reproduction 2012 May;27(5):1466-74. Epub 2012 Mar 13.

2. Gaskins et al. Human Reproduction 2012 Aug 11. [Epub ahead of print]

 

Jumping the Gun: Progesterone Levels Before Oocyte Retrieval and IVF Success

While every IVF clinic does things a bit differently, there is broad consensus that the two core components of “monitoring” response to medication during an IVF cycle include:

1. Blood estradiol
2. Follicle growth as measured by transvaginal ultrasound

That said, there are multiple reasonable approaches to IVF; some clinics also like to check other hormones, such as FSH, LH, and progesterone at certain times during the IVF stimulation.

Three recent studies (links below) highlight growing evidence supporting the importance of checking progesterone during an IVF cycle, particularly in the latter part of the cycle (after 6 or 7 days of medication). Progesterone is the hormone that causes the uterine lining to become receptive to pregnancy (“pro-” i.e. supporting, “gest” i.e. gestation/pregnancy). In normal physiology, progesterone is produced mainly by the corpus luteum, the structure resulting from the follicle after the egg has been released. By definition, therefore, progesterone action is timed by nature to kick in after ovulation, when a conceptus may be looking for a place to implant.

In an IVF cycle, however, due to the growth of multiple follicles (rather than just one, as nature would have it), progesterone levels sometimes start to rise prematurely – before ovulation, and even before the oocyte retrieval is performed. Early exposure to elevated progesterone levels is theorized by some to have detrimental effects on an embryo’s ability to implant. In other words, even the slight increase in progesterone levels caused by the IVF stimulation may throw off the synchronicity of the embryo and the lining enough to decrease chances of pregnancy.

There have been multiple studies aiming to address this subject in the past 10-20 years, and the results have been inconsistent. Many of these have been small studies using different cutoffs for what is considered an “elevated” progesterone level. Two of the studies cited below are amongst the largest ones that demonstrate a link between elevated progesterone and decreased chances of IVF success. The third, and perhaps most intriguing, takes this idea of “progesterone timing” even further and looks at the duration of progesterone elevation in addition to the amount. Taken together, I believe these studies warrant serious consideration when there is evidence of a premature progesterone rise prior to egg retrieval in an IVF cycle. While no studies address the question of what is the best plan of action in this situation, one logical option would be to forgo a fresh embryo transfer in order to allow the lining to “recover,” and plan for a frozen-thaw cycle with a healthy, well-timed lining 1-2 months later. 

1. Subtle progesterone rise on the day of human chorionic gonadotropin administration is associated with lower live birth rates in women undergoing assisted reproductive technology: a retrospective study with 2,555 fresh embryo transfers.
2. Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles.
3. The duration of pre-ovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles.