Typical Causes of Infertility: Are they treatable?

Approximately 12% of women (over 7 million) in the United States have had difficulty conceiving.  The causes are vast and in approximately 10% of couples, the causative factor is not clearly found despite a thorough evaluation.  Though modern advanced reproductive techniques such as in vitro fertilization (IVF) can allow over 90% of suitable previously “infertile” women to conceive, this comes with added levels of invasiveness, time involvement, stress, and cost.  Though IVF is the best choice for many couples and the fastest route to pregnancy for most, most women consider it as a last resort and try to exhaust other routes before proceeding to IVF.

How much of infertility issues are in control of the patient?  What can a couple do to ensure themselves the best possible outcome?  What can be done to protect themselves from possible future contributors to infertility?    I hope to briefly address these questions, discussing the most common causes of infertility, and how the woman (and the man!) can help themselves during the quest to start or enlarge their family.

Anovulation

One of the most frequent issues surrounding conception is anovulation, or the lack of regular ovulating cycles which produce fertilizable eggs.  Menstrual cycles occurring less than 24 or more than 35 days after the previous menses is most likely not associated ovulation.  It is not uncommon for a woman to have 1-2 irregular periods each year, but having less regular cycles than this is considered abnormal.  This abnormal condition occurs in 4-6% of all women and comprises approximately 40% of female fertility issues.

The heart of the matter in anovulation is an interference with the production or the effect of the brain’s chemical signaling to the ovaries.  This can be due to medical problems such as thyroid dysfunction, overproduction of certain hormones such as prolactin (normally involved with breast milk production), or androgens (the male sex hormones), or a lack of insufficient signaling from the brain to the ovary (termed Hypothalamic Anovulation).  The latter of these can be due to excessive stress, including physical stress (extreme over-exercising), lack of adequate caloric intake, and even common emotional stress, though there are serious medical causes that must be ruled out before heading off to that extra yoga class.

The most common cause of anovulation is Polycystic Ovarian Syndrome (PCOS) which affects approximately 10% of all women, and is thought to likely involve a genetic component.  Many people associate PCOS with obesity, however only about 50% of PCOS patients are obese.  The most current theory implies that most patients with PCOS suffer from some amount of resistance to the effects of their body’s produced insulin.  When secreted from the pancreas, insulin allows the cells in the body to utilize glucose as an energy source.  In the most severe cases, this is the cause of adult-onset (Type II) diabetes.   In essence, the patient is in an early pre-diabetic state.  This leads to elevated levels of insulin and overproduction of androgens from the ovaries and adrenal glands.  These effects, as well as irregular signaling of the ovary by the brain prohibit ovulation.  In addition, the excessively produced androgens can worsen the insulin resistance, thus feeding a vicious cycle.

Long term consequences of unregulated PCOS can include an increased risk of endometrial cancer, an elevated risk of early development of diabetes and cardiovascular disease, and sometimes excessive hair growth and acne.  For those not trying to conceive, the mainstay of treatment is oral contraceptive pills, with other treatments tailored to a patient’s clinical scenario.    Overweight patients with PCOS can often improve their insulin resistance with modest weight loss (5-10% of body weight) which can re-establish ovulation in some.   Though many patients with irregular cycles will have PCOS, a full investigation into other causes is warranted, and only after meeting certain criteria and ruling out all other causes can PCOS be diagnosed.

Continued research developments in understanding the cause, treatment of, and long term effects of PCOS makes the proper treatment a continually evolving concept.

Tubal Problems

Another common cause of infertility, equally as common as anovulation, is fallopian tube damage.   This may be damage which is induced (as in sterilization procedures) or acquired in other ways.  As many as one third of all patients undergoing a tubal ligation for sterilization will have regrets at some point in their future.  In some cases, reversal of a tubal sterilization can be performed.  In women with a good prognosis, microscopic tubal surgery to reattach the divided tubes can be very successful.  Conventional options for this include using a microscope to allow for an accurate tubal reconstruction.   A newer option is the use of the da Vinci Robotic Surgical System, which allows for a microsurgical repair using the minimally invasive laparoscopic surgery route, as opposed to the conventional method requiring an open incision.  However, for many women, having a tubal reversal is not the best route to conception.   This includes women over 37 years of age, those who had certain types of sterilization, and those who may have other contributing fertility issues.  These patients will be better served by proceeding directly to IVF, as their chance of benefiting from a surgical tubal repair is low and not cost effective.  It is best to seek the opinion of a reproductive endocrinologist to explore all of the procreative options and for a full discussion of all possible contributing factors prior to proceeding to surgical reversal.

The fallopian tubes can also be damaged in other ways, the most common of which is the prior exposure to an infectious organism.    As many as 40% of the general population, both male and female, has been exposed to Chlamydia in the past, though only approximately 6% report such a case.  This is due to many infections being “silent” and asymptomatic, being cleared by the body before a more serious pelvic infection sets in, but not before inflicting damage to the delicate tubes through scarring and inflammation.   In some cases, skilled reproductive surgeons can correct these damaged tubes through laparoscopic surgery, but in some cases, the tubes will not regain function, leaving IVF as the only realistic reproductive option.

Fallopian tubes can also be damaged by other inciting factors like a ruptured appendix, other extensive pelvic surgery, or a previous ectopic pregnancy.  Having tubal damage increases the risk of infertility and ectopic (tubal) pregnancies should one conceive.   Prevention is the best practice here, with condom use to protect against sexually transmitted infections being the most protective intervention.

Pelvic Disorders

Certain pelvic disorders can affect fertility.   These include uterine fibroids, endometrial polyps (growths of the uterine lining), and endometriosis.   Fibroids are very common benign tumors of the uterine muscle wall.  In some women, these may grow very large during the reproductive years, causing problems such as irregular bleeding or pain.  Fibroids can play a factor in infertility as well, especially if their size distorts the normal anatomy of the uterine cavity.  In this case, surgical removal is warranted. This can often be done in a minimally invasive route, often through laparoscopy on an outpatient basis.  Other alternative therapies marketed for fibroids such as uterine artery embolization (UAE), MRI-focused Ultrasound, or Cryomyolysis should not be performed on a woman who may desire future fertility.   Conceiving after having one of these procedures can impair fertility, as well as increase the risks to the pregnancy as well as the mother.

Endometrial polyps are commonly found in anovulatory and not uncommonly in normal cycling women.   Though they are often not the primary cause of infertility, they may be a contributing factor or may increase the chance of early miscarriage and thus should be removed.  This is simply done either as outpatient or in-office surgery.

Endometriosis is a disease in which the cells that make up the lining of the uterus (the endometrial cells) are located outside of the uterus.   Endometriosis is thought to exist in up to 15% of all women, though it is more commonly found in those with infertility, and appears to have a genetically-linked tendency.  The endometrial cells migrate out the fallopian tubes and into the pelvis during a menstrual cycle.  Here they skirt the body’s normal immune system, and are able to implant and grow within the pelvis, setting up areas of inflammation which can ultimately lead to distorting scar tissue.  This inflammatory state can contributes to significantly impaired fertility, which may be partially improved through surgical destruction of the endometriosis.  Though this is a continually progressive disease, the use of hormonal contraception such as oral contraceptive pills are recommended when not trying to conceive, as they provide a protective effect by suppressing the growth and continued development of endometriosis.

Age

One of the biggest contributors to infertility is the age of the woman.  Unfortunately, this is the one factor for which there is little treatment, regardless of therapy.   On average, normal fertility does not start to decline until around age 35, at which time is seen a slow decline in conception rates.   A sharper decline occurs after the age of 37, even more so after 40, realistically approaching zero after age 43.  It should be noted that this is an average, and some patients may experience a decline in fertility a few years earlier or later than average.  Because of this, it is recommended that any woman who has been unable to conceive for over one year, or any woman over the age of 35 who has been trying to conceive for longer than six months should be referred to a Reproductive Endocrinology & Infertility specialist for consultation and evaluation.  To date, there is no test that can give precise information about the state of a woman’s ovarian function, but several tests do exist that can give an estimate of this information.  However, many variables are involved and blanket interpretation can be misleading, thus this should be discussed with a Reproductive Endocrinologist prior to using these tests to guide decision-making.

Male Issues

Just as women can be affected with fertility problems, approximately 40% of infertility problems within a couple are due to a male issue.  This can include abnormalities with his sperm, including low sperm numbers, poor movement, abnormal sperm, or the absence of sperm.  These problems may be congenital or acquired.   Modifiable factors that can affect a man’s fertility include smoking (with marijuana being particularly harmful), excessive caffeine or alcohol intake, use of any steroid (prescribed or otherwise), chronic exposure to certain chemicals (such as pesticides or volatile chemicals), or chronic exposure to excessive heat (such as in routine sauna or hot tub usage).  It is recommended that any couple considering conceiving should eliminate potential harmful contacts, as production of new sperm after removal of an offending agent takes 2-3 months.  Obesity is another common factor which can affect a man’s sperm numbers through alterations in hormone profiles.   General evaluation of the man’s fertility can be as simple as obtaining a semen analysis, though laboratories associated with a infertility or urology practice should be utilized due to problems with test standardization.  Any abnormality justifies a repeat analysis in one month and a referral for an investigation by a urologist who has an interest in male infertility in conjunction with a Reproductive Endocrinologist.  Working together, they can actively make a recommendation and provide treatment that is in the best interest of the couple as a whole.  Treatment options range from eliminating offending agents, intrauterine insemination, in vitro fertilization, or the option of using donor sperm in some cases.

In conclusion, the protection of a couple’s fertility includes having an awareness of their current position in their reproductive lives, future conception plans, as well as an appreciation of the health and lifestyle issues that may impact their fertility.   

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