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  » Infertility  »  Unexplained Infertility

Unexplained Infertility


Unexplained infertility (also called idiopathic infertility) cases are those in which standard infertility testing has not found a cause for the failure to conceive . The definition of what "standard testing" consists of is not agreed upon by all experts.

Various studies have reported that 0-26% of infertile couples have unexplained infertility.The most commonly reported figures are between 10-20% of infertile couples.

In reality, there are hundreds (thousands ??) of "causes" of infertility. What I mean by this is that there are a lot of things that have to happen perfectly in order to conceive and have a baby. As a simplified example:

The hormones that stimulate egg development must be made in the brain and released properly

The egg must be of sufficient quality and be chromosomally normal

The egg must develop to maturity

The brain must release a sufficient surge of the LH hormone to stimulate final maturation of the egg

The follicle (eggs develop in structures called follicles in the ovaries) must rupture and release the follicular fluid and the egg

The tube must "pick up" the egg

The sperm must survive their brief visit to the vagina, enter the cervical mucous, swim to the fallopian tube and "find" the egg

The sperm must be able to get through the cumulus cells around the egg and bind the shell (zona pellucida) of the egg

The sperm must undergo a biochemical reaction and release their DNA package (23 chromosomes) into the egg

The fertilized egg must be able to divide

The early embryo must continue to divide and develop normally

After 3 days, the tube should have transported the embryo into the uterus

The embryo must develop into a blastocyst

The blastocyst must hatch from its shell

The endometrial lining of the uterus must be properly developed and receptive

The hatched blastocyst must attach to the endometrial lining and "implant"

Many more miracles in early embryonic and fetal development must then follow...

A weak link anywhere in this chain can cause failure to conceive

The above list is very oversimplified, but the point is made. There are literally hundreds of molecular and biochemical events that have to function properly in order to have a pregnancy develop. The standard tests for infertility barely scratch the surface and are really only looking for very obvious factors, such as blocked tubes, abnormal sperm counts, ovulation regularity, etc. These tests do not address the molecular issues at all. That is still for the future...

The likelihood of a diagnosis of unexplained infertility is increased substantially in women 35 and over - and greatly increased in women over 38. The reason for this is that there are more likely to be egg quantity and quality problems as women age. Since we do not have a "standard category" called egg factor infertility, these couples sometimes get lumped in to the "unexplained" infertility category.

Some experts would also consider infertility associated with mild endometriosis to be in the "unexplained" category. This is because a cause and effect relationship has not been established between mild endometriosis and infertility.

Prognosis for untreated couples with unexplained infertility

The duration of infertility is important:

The longer the infertility, the less likely the couple is to conceive on their own. After 5 years of infertility, a couple with unexplained infertility has less than a 10% chance for success on their own.

One study showed that for couples with unexplained infertility of over 3 years duration, the cumulative conception rate after 24 months of attempting conception without any treatment was 28%. This number was found to be reduced by 10% for each year that the female is over 31.

(Reference: Collins, JA and Rowe, TC. Fertility and Sterility 1989;52:15-20.)

Treatment for unexplained infertility

Ovarian stimulation and/or intrauterine insemination

Intrauterine insemination vs. timed intercourse

This has been studied and a slight improvement found for insemination. However, the difference was not large enough to be statistically significant.

Clomiphene citrate

3-6 months of treatment might improve fertility by as much as 2 times as compared to no treatment. This is a very low level infertility treatment. Infertility specialists do not usually recommend this level of treatment for women over the age of 35-37. Some do not use it on any couples with unexplained infertility.

Injectable gonadotropins plus i ntrauterine insemination

Several studies showed improved pregnancy rates with this treatment as compared to no treatment.

Injectable gonadotropins plus intercourse

This is less extensively studied. It is not yet known whether the ovarian stimulation and the insemination have independent beneficial effects or whether their beneficial effects are only seen when they are used in combination.

Assisted reproductive technologies as treatment for unexplained infertility

In vitro fertilization (IVF) has high success in young women with normal ovarian reserve testing and unexplained infertility.

Our IVF pregnancy rates

IVF also can give us clues as to the cause of the infertility. For example, we may see low fertilization rates per egg, or we may see slow embryo development, excessive fragmentation of the embryos , abnormal eggs , abnormal egg shells (zona pellucida), etc...