Dr. REBECCA B. SINGSON, M.D., FPOGS

Research shows that approximately 90% of couples should conceive within 12 months. Once a couple actively starts work on having a baby, and no pregnancy occurs after one year of unprotected intercourse, they are considered infertile.

THE AGE FACTOR

If you are already in your thirties and still focused on climbing the corporate ladder or amassing wealth you can retire on before pondering a pregnancy, hear this. There has been a documented decline in a woman’s ability to get pregnant in the early thirties and there is a further decline once you hit your late thirties and early forties. Approximately 1/3 of women from age 35-44 cannot get pregnant anymore. It is interesting to note that in studies of tribal communities with large families who do not practice any contraception, fertility peaks by age 25 then rapidly declines after 35 years of age. This age-related decline in fertility appears to be because of the drop in the number of eggs in the ovaries, as well as a possible drop in the ability of these eggs to get fertilized. One simple test of this is a rise in the level of FSH (follicle stimulating hormone) secreted at the base of the brain whose job is to shout to the ovary to release an egg. Women whose FSH levels rise above 15 mIU/ml on the 3rd day of the menstrual period have been found to have reduced pregnancy rates even with the help of in vitro fertilization (IVF). Its as if the brain signals to the ovary to release an egg but with no response, the brain keeps sending more and more signals to the ovary in the form of FSH so the level of FSH rises.

The interesting fact, however, is if an older woman desiring fertility is implanted with an embryo produced from eggs retrieved from younger women, the older woman is able to achieve a pregnancy. This is where the elderly woman can turn to her younger sister (preferably in her 20’s) for a life-changing generous “donation” in the form of oocytes. The pregnancy rates among recipients of donor oocytes remain relatively constant until 50 years of age. This strongly suggests that it is the age of the egg, rather than the age of the uterus that is responsible for decline of fertility in the aging woman. So if you’re still thinking about delaying your pregnancy, think twice and consider your age.

THE SPERM FACTOR

In pregnancy, as with many other things, it takes two to tango. Infertility is always a problem of the couple yet many woman come to the clinic seeking fertility work-up without their spouses. Women always think they are to blame if they cant get pregnant but the fact is, in 25-40% of the case, it is the husband ‘s fault. In fact, the sperm count is one of the cheapest (P800 or less) and most basic diagnostic tests in evaluating an infertile couple. It is alarming that the sperm count in males have dropped substantially over the past 50 years suggested to be associated with increased levels of environmental toxins in the last half of the 20th century. Cocaine, marijuana, cigarette smoking and heavy coffee consumption all diminish semen quality. Therapeutic drugs such as steroids, cimetidine, erythromycin, nitrofurans, spironololactone and tetracycline may also reduce sperm counts. Varicocoeles (abnormal dilatation in veins within the spermatic cord) have been blamed for male infertility but evidence-based research has shown that performing varicocoelectomy has not demonstrated to increase fertility rates. As long as there are five to 10 million good sperms, the couple may be greatly helped with artificial insemination where only the good sperms are harvested and inserted to the womb of the female. If there are less than 5 million good sperms the couple will have to resort to in-vitro fertilization (IVF). As long as there is one good sperm, this can be injected by intracytoplasmic sperm injection (IVF-ICSI) into the egg harvested in the female to create an embryo. There are even azoospermic (no sperms at all) males who can be helped by doing a testicular biopsy, obtaining the live sperm and injecting it into the egg to be fertilized, a process called TESDA.

OVULATORY FACTORS

If I would choose from among the different causes of infertility to be inflicted with, it would be this because it is the easiest to diagnose and the easiest to treat. Ovulation factors account for about 20% of all infertility.

The basal body temperature (BBT) is the simplest, most non-invasive means to determine ovulation. It entails taking the temperature as soon as the woman wakes up before any physical activity, using an ovulation thermometer. The temperature is charted daily, indicating any episodes of bleeding, staining, and intercourse. When there is a drop or dip in the temperature of at least 0.1*F (0.06*C) lower than the 6 previous days ,ovulation is imminent and the couple should have intercourse. A sharp rise of 0.4*F to 0.6*F (0.22*C to 0.33*C) between two consecutive days signals ovulation. This procedure can be tedious for some women since it entails taking the temperature daily. For some, using the ovulation kit is more convenient. Ovulation usually occurs 16-48 hours after the surge of the leutinizing hormone. The kit can be helpful in timing pregnancy or insemination. Another common method to monitor ovulation is by vaginal ultrasound to monitor the growth and progress of the egg in the ovary, called follicle monitoring ultrasound,

Many infertile women do not realize they have Polycystic Ovary Syndrome (PCOS). These women do not release an egg monthly and therefore have irregular periods, may show signs of high levels of male hormone as reflected by increased facial or body hair, obesity or acne, and ultrasound of the ovaries may show many small cysts. Evaluation to establish diagnosis should be made since women with PCOS can get pregnant if given ovulatory drugs like clomiphene citrate, as well as metformin (yes, a drug given to diabetics) to reduce the metabolic abnormalities leading to obesity and increased circulating male hormones.

Three to 14% of women can actually have what is called Luteal Phase Defects which means that the lining of the uterus does not correspond with how it should appear microscopically for that day of the cycle. This can happen when the progesterone released by the ovary after the egg is released is not high enough. Factors that may contribute to this are thyroid problems, over- or underweight, exercise, stress, drugs, among other problems. This is diagnosed by endometrial biopsy or by doing progesterone assays. Progesterone intravaginal gels or injections are available in the market to solve this problem.

CERVICAL FACTORS

In 5-10% of cases, cervical factors can cause infertility. Towards the day of ovulation, the cervix becomes clear and sticky like egg white. Clear, watery mucus without white blood cells was found to bring about higher pregnancy rates than thick, cloudy mucus with many white blood cells. White blood cells may be cause by cervical infections which may be given appropriate treatment if proper diagnosis is made. Clomiphene citrate, given to induce ovulation, can actually make the cervix unfavorable for sperm to enter because but giving estrogen supplements has been found to actually solve the problem.

TUBAL FACTOR IN INFERTILITY

In 30% of patients who cannot get pregnant, there may be problems with the fallopian tube. If a patient has had a ruptured appendix or a septic abortion, an ectopic pregnancy, a previous pelvic or tubal surgery, a history of pelvic inflammatory disease or has use an IUD, the chances of a tubal problem increases in an infertile patient. If the patient has had multiple sexual partners, the chances of having chlamydial infection increases as well. Chlamydia is a sexually transmitted disease which may produce silent damage on the tubes, meaning the patient is unaware that she is infected yet the disease is damaging her fallopian tubes. After one episode of chlamydial salpingitis (infection of the fallopian tubes with Chlamydia), the incidence of infertility is 11-12%. After 2 episodes, the incidence increases to 23% and after 3 episodes, 54%. The relative risk of tubal infertility is 2.6 fold greater for women who ever used an IUD compared with those who never used one. Women who had only one sexual partner had no increased risk of primary tubal infertility associated with IUD use. Tubal problems can be evaluated by doing a hysterogram (using a fluoroscope) or a sonohysterogram (using an ultrasound) or by laparoscopy under direct visualization. In a hysterogram, a dye is injected through the cervix using a cannula under fluoroscopic guidance to determine if the tubes are open and if there are any distortions in the uterine cavity. A sonohysterogram involves the same procedure using an ultrasound instead of x-ray guidance.

UTERINE AND PERITONEAL FACTORS

The chances that a woman might be infertile due to uterine factors is only 2%. Myomas, which are benign tumors in the muscle of the uterus, are the most notorious for causing distortions in the uterine cavity. Not all myomas need to be removed in case of infertility. The obstetrician needs to evaluate if the myoma is large enough to cause infertililty either by competing for blood supply with the embryo or causing distortion of the uterine cavity or blocking the entrance to the fallopian tube. In patients who have had a history of a previous D & C for a miscarriage, the uterus might be overcuretted causing adhesions on the uterine lining, preventing the sperm from reaching the tubes. This is a rare occurrence but in such instances, the adhesions may be lysed and an IUD placed to prevent the adhesions from recurring.

UNEXPLAINED INFERTILITY

Unexplained infertility is diagnosed when a woman has had at least 2 years of infertility despite a normal history and physical examination, having adequate sexual contact with a partner with a normal sperm count, regular monthly menstrual cycles with evidence of ovulation, adequate luteal phase of the menstrual cycle of at least 12 days, normal bacteriologic cultures, immunologic tests, hormonal profile, and ultrasound studies.

Immunologic factors
Immunologic factors have been found in upto 40% of couples with unexplained infertility. It remains controversial even among infertility experts but it may result from depletion or destruction of sperms or inhibition of transport of sperm in the female genital tract. In males, vasectomy, testicular torsion, or trauma, or an infection, can result in an immunologic reaction that can cause formation of antisperm antibodies. Women who undergo artificial insemination, on the other hand, can develop antisperm antibodies. Infection or inflammation may also increase the probability that sperm will interact with the body’s immune system components.

APAS Syndrome is another controversial disease entity which not all infertility experts are in agreement with. Essentially, it is caused by the mother producing antibodies against phospholipid antigens resulting in clotting of veins and arteries supplying the embryo, causing failure of implantation of the embryo. A blood test to check for a panel of antibodies can clinch the diagnosis. A reproductive immunologist is very helpful in managing these problems when diagnosed.

Infection
Subclinical infections have been known to cause infertility over the past 30 years. Mycoplasma are microorganisms as small as a large virus but have no cell walls. Research has shown a greater prevalence of genital mycoplasma in cervical mucus and semen of infertile couples compared to fertile couples. The two kinds of mycoplasma commonly recovered are Mycoplasma hominis and Ureaplasma urealyticum. There is evidence that the sperm counts of men positive for ureaplasma tend to have more abnormal sperms with poor motility. The quality of the sperm has been found to improve after antibiotics therapy to eradicate ureaplasma. This is not universally documented though and upto 50% of men with normal sperms have been found to be positive for mycoplasma cultures. Controversial as it may seem, it is still considered prudent to treat patients with positive cultures with either doxicycline or tetracycline before any invasive procedures are planned on an infertile couple.

Luteinized Unruptured Follicle (LUF)
This phenomenon means that the woman’s ovary goes through the selection of an egg to be released, makes it grow in size with the proper release of hormones, but in the end, the egg never leaves the ovary so there is no chance to meet the sperm in the fallopian tube. The ovum remains in the ovary and regresses there. It is unkown why this happens and it is difficult to predict to whom it will happen, and in many cases is even difficult to prove the diagnosis. Research shows that LUF Syndrome is more common in women with endometriosis or pelvic adhesions and after clomiphene citrate therapy.

It is important for the patient to recognize when it is time to seek professional medical care in cases of infertility while the chances are good for the woman to get pregnant. As the woman ages, fertility becomes a race against time. The infertility specialist can help not only to evaluate but to treat and to counsel as well. You can be informed when it is time to go for assisted reproductive techniques, or to go for adoption and other alternatives or to be directed to various social support systems available to the community. Don’t wait to look back to an infertility work-up and say, “ I should have done it when I was younger”.