Last week a patient presented to my office with a question that made me feel like I was responding to a Dear Abbey letter requesting help to make some crucial life decisions that were related to her reproductive health.  As I pondered her query that I had heard so many times before I wondered how terribly nerve racking it must feel like for this woman.

Dear Fertility Doc,

“I am 39 years old, single and I enjoy my career.  However, I always dreamed I would have children.  Unfortunately, I have not yet met a man that I would feel comfortable with to marry and with whom to have a baby.  What should I do?”

Signed,

At Reproductive Crossroads

The issues that this woman brings up are universal in my practice.  She basically has to weigh her desire to have children now rather than delay, using her own eggs or potentially with an egg donor or to adopt.   She needs to consider the ramifications of taking time off from her career as well as creating a child with donor sperm.  She expressed concern to me that if she were to meet Mister Right how will he respond to this child?  Are there any tests that I can perform that can help this woman make a decision?

First of all, it is imperative in cases like this to do a full fertility screen so that we understand from a fertility perspective how much time she has left and how urgent this patient needs to make a decision.  To assess her fertility I do a Day 3 serum Estradiol and FSH, an AntiMullerian Hormone and a sonographic antral follicle count.  The FSH is regulated by negative feedback from serum Estradiol and inhibin both of which are produced by the granulosa cells of the ovarian follicles.  With diminishing ovarian activity there are fewer follicles, less estradiol and inhibin so with less feedback, the FSH level is high.  Occasionally, in patients with low ovarian activity, often called reserve, a patient may have an ovarian cyst that produces estradiol.  This will lower the FSH level to otherwise normal activity levels even when there is minimal ovarian activity and inhibin.  One would misinterpret the low normal FSH in the presence of higher estradiol which is why this must be measured concurrent with FSH.

AntiMullerian Hormone is also produced by the granulosa cells and low levels therefore indicate depleted ovaries.  Likewise, few antral follicles seen on ultrasound typically performed during the early follicular phase of the cycle will indicate low ovarian reserve.

Once we know a patient’s relative fertility through this screen we need to decide whether she is prepared to delay her career for pregnancy and motherhood or should she do IVF and freeze her embryos thereby freezing her fertility potential at the current state.

Since she is single without a participating partner we would be using the sperm from an anonymous donor.  The specimens are obtained from sperm banks that are certified by New York State by virtue of their screening and testing for infectious and hereditary diseases.  Patients may review what is available from the sperm banks.  They can review on the internet the donor’s demographic information, physical attributes, educational and occupational histories, etc for the offered specimens.

If a woman does not have any infertility issues I would attempt donor insemination.  However, due to her advanced age, I would progress to more aggressive therapies if we were not successful after a few cycles.

A common concern for women in this circumstance is that they may meet their soul mate in the future and he may not be comfortable with a child produced with someone else’s sperm.  This is an issue that is very individual and I can only offer to support the patients as they decide what is best for them.

As she prolongs the decision her fertility is diminishing, and thereby risks not being able to have a child using her own eggs.  If conceiving with one’s own eggs is crucial then she must weigh the downside of conceiving a child from an anonymous donor and if she does so, the potential problems associated with finding a man in the future who she may want to have a family with.

It is enormously stressful making these decisions at these reproductive crossroads.

I discuss these issues with my patients and help them arrive at the decision that is right for them.

Sperm Meets Egg

Why me? My wife never had an infection, surgery or any other problem? I have no difficulty ejaculating and there’s plenty to work with so why can my friends, neighbors and coworkers get pregnant and we can’t?

I hear these questions daily and appreciate the frustrations, anger and stress felt by my patients expressing these feelings through such questions. There are many reasons why couples do not conceive. An infertility workup will identify some of these. A semen analysis will pick up a male factor in 50-60% of cases and in more than half of these cases the male has the only problem. An hysterosalpingogram will locate tubal disease in about 20% of cases. Another 20-25% of women do not ovulate or ovulate dysfunctionally preventing conception.

Even when a semen analysis is normal it is possible that a post coital test may identify that the problem is that the sperm is not reaching the egg. It may not be able to swim up the cervical canal into the womb and up the tubes where it should normally find an egg to fertilize. When these tests are normal a laparoscopy may be performed to identify the 20-25% of infertile women with endometriosis. However, even when the infertility workup is normal and there is no test that logically explains the lack of success in achieving a pregnancy; an IVF procedure may both identify the cause as failure of the egg to fertilize and treat it successfully by injecting sperm microscopically into the egg by a procedure called Intracytoplasmic Sperm Injection or ICSI.

What causes male factor infertility?

There are several potential causes of male factor infertility. Hormonal causes can be caused because of problems at the hypothalamic-pituitary level or at the testicular level. Normally, the hypothalamus regulates pituitary production of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). FSH and LH drive the testis to produce sperm and testosterone. Deficiency of FSH or LH can lead to lack of ability to drive the testicular production of sperm and testosterone just as lack of gas will prevent a car from being able to run. Today, the most common reason for a man to have FSH and LH production shut off is from his use of anabolic steroids such as testosterone, hcg (human chorionic gonadotropin) and clomiphene (clomid). These all may provide negative feedback on the pituitary turning off FSH and LH production. One can also see elevated testosterone shutting down the testis with congenital adrenal hyperplasia and adrenal tumors.

Pituitary tumors, infarction, surgery, radiation and infiltrative processes can also diminish FSH and LH production. In the presence of low FSH and LH it may be useful to check for elevated prolactin levels to rule out a pituitary prolactinoma and obtain an MRI to check for other tumors or pituitary pathology.

Isolated deficiency of LH and FSH can occur (Kallmann’s syndrome) and lead to diminished testis (hypogonadism). This occurs in 1 in 10,000 men. Less common defects are seen in hypothalamic stimulation of the pituitary and are usually associated with other congenital findings.

Abnormal thyroid and glucocorticoid (prednisone) excess can result in decreased spermatogenesis through effects on the hypothalamus and LH production or conversion of androgens (male hormone) to estrogens.

Testicular causes include the presence of tumor, chromosomal abnormalities, congenital absence of germ cells, drugs and radiation that are toxic to the testes, undescended testes and varicocoele.

Ten per cent of males with a sperm count under 10 million and 20% of men with azospermia have a chromosomal abnormality. Kleinfelter’s syndrome is a genetic disorder due to the presence of an extra x chromosome in the male. This occurs in 1 out of 500 males and is often seen in the mosaic form where some cells are 46 xy and some are 47 xxy. The testes tend to be small and these men have delayed sexual maturation, azospermia and gynecomastia (enlarged male breasts). There has been some success with ICSI of biopsied immature sperm cells.

Sertoli-cell only syndrome or germinal cell aphasia may have several causes including congenital absence of the germ cells, genetic defects or androgen resistance. Testicular biopsy shows complete absence of germinal elements. Men are azospermic yet virilize normally. Testes may have normal consistency but be slightly smaller in size. Testosterone and LH levels are normal but FSH is usually elevated. Men with testicular failure secondary to mumps, cryptorchidism or radiation/chemotherapy damage have smaller testes with a non uniform histologic pattern. The testes may have severe sclerosis and hyalinization. There is no treatment for this form of azospermia.

Gonadotoxic drugs like chemotherapy or radiation can effect the germinal epithelium because it is a rapidly dividing tissue and is susceptible to the interference imposed by these toxins on cell division. At radiation exposure below 600 rads, germ cell damage is reversible. Recovered spermatogenesis may take up to 2-3 years even when exposed to low doses of radiation. Elevated FSH levels reflect the impaired spermatogenesis and return to normal once the testes recover.

Orchitis occurs in 15-25% of males who contract mumps which is unilateral in 90% of cases. Testicular atrophy may take years to develop. At least two thirds of men with bilateral orchitis remain infertile for life.

Trauma either through accident or torsion of a testis is a relatively common cause of subsequent atrophy with potential diminished fertility.

Medical conditions such as renal failure, cirrhosis of the liver and sickle cell disease can all lead to low testosterone levels and decreased spermatogenesis.

Cryptorchidism occurs in 1 in 12 males. The undescended testis becomes abnormal after age 2. Even when unilateral, cryptorchid patients have reduced fertility potential.

The varicocoele is the most common finding in infertile men. It is the result of backflow of blood due to incompetent valves in the spermatic veins. 90% occur on the left and is found in 20% of males 40% of the infertile population. 50% of men with varicocoeles are fertile. It is thought that a varicocoele can cause infertility by elevating the temperature of the testis. Varicocoelectomies however are not universally helpful and remain somewhat controversial for many cases of infertility.

Unfortunately, at least 25-40% of infertile men have idiopathic infertility for which no cause may be identified.

Other causes of azospermia include congenital absence of the vas deferens or obstruction secondary to infection or surgery. These cases may be amenable to surgical reconstruction and/or ICSI with epididymal aspiration or testicular biopsy to obtain sperm. These are the most successful cases of ICSI associated with azospermia.

Sperm antibodies may be a relative cause of infertility in about 3-7% of cases. Treatment has been successful with intrauterine insemination and with ICSI.

Infections can affect sperm motility secondary to e coli, Chlamydia, mycoplasma, ureaplasma and trichomonas. Culture and treatment for asymptomatic infertile males remains controversial.

Sexual dysfunction is a presenting cause of male infertility in about 20% of cases. Decreased sexual drive, erectile dysfunction, premature ejaculation and failure of intromission are all potentially correctable causes of infertility.

Treatment of Male Infertility
Treatment depends on diagnosis. In cases where the FSH and LH are low with a normal head MRI, clomiphene may be of benefit. Clomiphene citrate (Clomid or Serophene) is one of the most widely used drugs in male infertility. It is a weak anti-estrogen that interferes with the normal feedback of circulating estrogens and results in an increase in GnRH that stimulates gonadotropin secretion. The resulting elevation in LH and FSH increases intratesticular testosterone levels and in theory should improve spermatogenesis. Gonadotropin therapy may be used if clomphene is unsuccessful in the face of low FSH and LH.

If a pituitary tumor is found, surgery or medications to lower prolactin may restore spermatogenesis to normal.

An obstructed vas may be microsurgically reconstructed. Surgery may also be performed in the presence of a varicocoele.

Intrauterine insemination may improve delivery of sperm to an egg or in the absence of any sperm, artificial insemination with donor sperm is often successful.

Intracytoplasmic sperm injection into the egg in an IVF procedure is highly successful when sperm may be obtained through the ejaculate and even through testicular biopsy. When normal mature sperm are rare such as in testicular failure, associated with elevated FSH, ICSI is much less likely to result in fertilization and pregnancy. Immature sperm cells rarely can result in a healthy pregnancy.

Naturopathic Treatment

Naturopathic treatment for male infertility focuses on improving sperm quantity, sperm quality, and overall male reproductive health. There have been reports that sperm counts have fallen almost 50% since the 1930s. Although some dispute these findings, it is generally accepted that sperm counts are declining. The cause may be environmental and dietary and lifestyle changes may interfere with men’s sperm production. If this is so, improving diet and making healthy lifestyle choices should positively impact male reproductive health.

Nutrition

The importance of a healthy diet cannot be overstated. To function properly, the reproductive system requires the proper vitamins and minerals. Nutritional deficiencies can impair hormone function, inhibit sperm production, and contribute to the production of abnormal sperm

• Eat a natural foods diet that focuses on fresh vegetables, fruits, whole grains, fish, poultry, legumes, nuts, and seeds.
• Drink 50% of body weight in ounces of water daily (e.g., a 150 lb man would drink 75 oz of water).
• Eliminate processed and refined foods (e.g., white flour), junk food, sugars, alcohol, and caffeine.
• Avoid saturated fats and hydrogenated oils (e.g., margarine); use olive oil.
• Pumpkin seeds are naturally high in zinc and essential fatty acids which are vital to healthy functioning of the male reproductive system. Eat pumpkin seeds to help maintain a healthy reproductive system.

Supplements

The following supplements may increase sperm count and/or motility. Allow 3-4 months for the supplements to work. The following is a list of supplements with their supposed benefit.

• Arginine – Take 4 gr daily. Needed to produce sperm. If the sperm count is below 10 million per ml, arginine probably will not provide any benefit.
• Coenzyme Q10 – Take 10 mg daily. May increase sperm count and motility.
• Flaxseed oil – Take 1 tbsp daily. Is a source of essential fatty acids.
• L-carnitine – Take 3-4 grams daily. Required for normal sperm function.
• Multivitamin-mineral – Buy a high-quality product and take one serving size (differs from brand to brand).
• Selenium – Take 200 mcg daily. May improve sperm motility.
• Vitamin B-12 – Take 1000 mcg daily. A B-12 deficiency reduces sperm motility and sperm count. Even if no deficiency exists, B-12 supplementation may help men with a sperm count of less than 20 million per milliliter or a motility rate of less than 50%
• Vitamin C – Take 500 mg 2 times daily. Is an antioxidant.
• Vitamin E – Take 400 IUs 2 times daily. Is an antioxidant and may improve sperms’ ability to impregnate.
• Zinc – Take 30 mg 2 times daily. Required for a healthy male reproductive system and sperm production.

Herbal Medicine

Herbal remedies usually do not have side effects when used appropriately and at suggested doses. Occasionally, an herb at the prescribed dose causes stomach upset or headache. This may reflect the purity of the preparation or added ingredients, such as synthetic binders or fillers. For this reason, it is recommended that only high-quality products be used. As with all medications, more is not better and overdosing can lead to serious illness and death.

The following herbs may be used to treat male infertility:

• Ginseng (Panax ginseng) – Known as a male tonic (an agent that improves general health) and used to increase testosterone levels and sperm count. Siberian ginseng (Eleutherococcus senticosus) may also be used.
• Astragalus (Astragalus membranaceus) – May increase sperm motility.
• Sarsaparilla (>Smilax spp.) – Known as a male (and female) tonic.
• Saw palmetto (Serenoa repens) – Used for overall male reproductive health.

Other Recommendations:

Avoid alcohol. Alcohol consumption is associated with an increased number of defective sperm.
• Consider acupuncture.
• Do not smoke, or quit smoking. There is an association between smoking and low sperm count, poor sperm motility, and abnormal sperm.
• Proxeed – is a new nutritional supplement that may improve sperm health and fertility rates. The ingredients include L-carnitine and acetylcarnitine, two vitamin-like substances synthesized naturally by the body. These chemicals are involved in cellular metabolism and are found in semen at a rate that is proportionate to the amount of healthy sperm. Proxeed is purported to improve sperm count, concentration, and motility when taken orally for about 2 months. It is reported that approximately 30% of couples using it conceive. It is available without a prescription, although couples considering it should consult their physician.