Demographics and Epidemiology

The traditional definition of infertility is twelve months of unprotected sexual intercourse without establishing a successful pregnancy. This definition was derived in studies showing that 90% of couples will achieve a pregnancy during that time frame. Approximately 50% of otherwise healthy reproductive age women should be pregnant in the first three or four months of attempts. About 70% should be pregnant by six months and of the remaining 10% not pregnant after twelve months, still about one third will become pregnant in the following two years. It is, however, an injustice to our patients not to discuss of fertility at routine health visits, or to wait a year before starting education and counseling.

It seems perfunctory to begin any discussion of infertility by stating that about one in six American couples is infertile. The true incidence of infertility is not known. It is estimated that over 50% of infertile couples never seek therapy. When taking medical histories for problems unrelated to infertility, it is commonplace to hear of years of attempts before a pregnancy is successfully established or in between pregnancies. A useful exercise is to imagine 50% of the couples with no children are childless not by choice.

It has been debated whether the incidence of infertility is increasing. Certainly, there are two trends that may add to a definite increased risk of infertility. The first of these is that the number of sexual partners has increased and with this, the risk of pelvic infection and subsequent tuboperitoneal disease. The second of these is delayed child bearing.

Many women are postponing childbearing until the late 20's to late 30s while other life objectives are met. Maximum female fertility occurs in mid-twenties at a time when menstrual cycles are most regular and ovulatory. Before age 20 and after age 30, fertility is slightly decreased and individuals under over age 37 are much less fertile. Presently, age forms our largest barrier to successful fertility therapy.

The mind set

There are several mistakes commonly made in the approach to the infertile or potentially infertile couple. The first is to assume that for a young couple are still "kids" and that there is plenty of time to start a family. Once it has been decided that a pregnancy is desired, it becomes a foremost and very pointed pursuit. The strength of this desire is unrelated to age, social class, or etiology of the infertility. A second mistake has been a dismissal by physicians by patients who want to discuss the possibility of infertility even though they have only tried for several months. "Go home and relax there is plenty of time" is never an answer. There is no time too soon to discuss the basics of the normal menstrual cycle and ovulation testing. If a specific history is obtained of menstrual cycle irregularity, potential male factor, or if the female partner is over age 35, there should be no delay in the first stages of an infertility investigation. Assume that women over 35 have a significant decrease in their fertility. Assume that women with cycles over thirty-five days apart are not ovulating well and that it is a waste of time to spend in detection of ovulation. When to begin therapy or intensive an investigation is related to each individual case. Although not universally true, many couples can be comforted by knowing that Infertility in women under age 38 is imminently treatable. Education and information can be significant stress reducers.

Men and women handle the stress of infertility differently. Women may become so preoccupied with their fertility that it is the first thing thought of arising in the morning and the last thing before sleeping at night. It will often seem that every other female with whom she comes in contact is pregnant, or has recently had a child. This is often translated into the pregnant women are successful and I'm a failure. There is a feeling of helplessness and hopelessness often with self-imposed isolation. Males typically address the fertility issue differently, but it is a mistake to believe they are ambivalent or do not have very strong feeling about childbearing. Women are often the first to want to become pregnant, first to seek therapy and first to want to move to aggressive therapy. If a woman is told that she doesn’t ovulate, she will say “fix it,” while male told of sperm count is low may result in an emotional meltdown. Men often identify semen parameters with potency and potency with virility.

Some couples will rebuke any attempt at any intervention on the psychological and emotional aspects of therapy. Some will seek to compensate by learning of every new technique and the possibility of therapy. Psychological services are becoming increasingly and specifically available for infertile couples. These may take the form of a psychologist or support group. Very often infertility patients are using the Internet where they correspond with numerous individuals and may participate in chat rooms. It is impossible to know of the toll that stress takes on infertility. Stress itself has not been shown to conclusively alter success rates. However, reduction of stress can easily be translated in reduction of emotional suffering and therefore it should be a therapeutic goal.

Preconception Counseling

Preparing for a pregnancy can not only improve the safety of the pregnancy for both mother and baby, but it could even improve fertility.

• Folic acid supplementation (I recommend 1 mg daily) added to a standard multivitamin.
• Glucose tolerance test with fasting and 1-hr insulin levels, in PCOS patients, or those at risk for diabetes.
• Achieve maximum nutritional status possible while avoiding stringent dieting and overly aggressive physical activity.
• No tobacco use. (both partners) Smoking has clearly related to decreased egg and sperm quality. Avoid use of nicotine supplements. Bupropion (category B) has a good safety profile although data is limited.
• Consume alcohol and caffeine in modest amounts. (studies are inconclusive and recommendation should be individualized).
• Rubella vaccination, if not immune
• Hepatitis B vaccination, if at social or occupational risk.

Oral contraceptives - The regular pattern of bleeding while using OC’s give a false impression of normalcy and masks underlying ovarian dysfunction. The pill does not cause infertility or ovarian dysfunction. To the contrary it may protect fertility by decreasing risk of uterine fibroids, endometriosis, pelvic inflammatory disease, and possibly preserving ovarian function. A personal opinion is that pregnancy should be attempted in the first month after the pill is stopped. The so-called “wash-out” period may be a time of greatest fertility. Immediately after the pill is stopped, there can be a rebound effect resulting in a window in which ovulation occurs. The miscarriage rate may be slightly higher in conceptions established during the first month off the pill, but an attempt at pregnancy may be a calculated risk worth taking.

The fertile period - It's amazing how much misinformation there is about timing intercourse. Ovulation occurs toward the end of a 5-7 day time span called the fertile period. In an idealized 28-day cycle, ovulation occurs on days 13-15. If the cycles vary within the acceptable 26-32 day range, the fertile period is from days 11-16. If intercourse occurs three times during the fertile period there is probably adequate exposure. It doesn’t matter if there are two or three days in a row, or even several days without intercourse. Chances are that over several months the timing will be perfect. Sperm require up to six hours in the female reproductive tract before they develop the capacity to fertilize an egg, so plan ahead. Intercourse every day may reduce sperm counts, while intervals of over three days may miss ovulation. The goal is to have healthy sperm at the site of fertilization awaiting ovulation. Once released from the ovary, the life span of an egg is short, probably 12-24 hours. However, sperm remain capable of fertilization for at least two days. "Over-timing" heightens anxiety and lessens the sexual bond.

Coital position - The second most common question after when to have sex is how to have it, or about coital position. The answer, change position for recreation, not procreation. There are many different sexual positions and many different positions of male and female anatomy. There may be one best for an individual couple, but not one best for everyone. There is no informative abut activity after intercourse, but a controlled trial after artificial insemination has shown improves rates when there was a 10-15 minute rest period after insemination. Often couple are concerned that the semen seems to "run out" after intercourse. The first and best part of the ejaculate is naturally placed in the deepest portion of the vagina and is least likely to be lost. Usually the discharge is form semen liquefaction. Women also frequently ask "could my body be killing sperm?" Possibly, but this is an uncommon cause of infertility and since antibodies are located in the cervix, one that is usually easily bypassed by intrauterine insemination.

Requirements of Reproduction

There are four basic requirements for reproduction, and therefore four areas for investigation as to the cause of infertility.

1. A sperm
2. An egg
3. Open passages to allow the egg and sperm to meet
4. A uterus to nurture the developing pregnancy

A sperm = It only takes one

It is thought that about 40% of infertility is due to male factors. Specific questions regarding previous and present illnesses, medication use, smoking and alcohol use, surgery, illnesses, infections, and environmental exposure should be determined. About 5% of men with severe alterations in semen quality with have a hereditary microdeletion of the x chromosomes. Often thee is a family history of infertility and a careful family history should be taken as a part of the initial fertility evaluation. A physical examination may reveal abnormalities of the reduced testicular volume or varicocele.

Semen analysis and ovulation detection. If there is a single test that is most important in determining origin of infertility, it is a semen analysis. The semen analysis represents an integrative test of both hormonal functioning and sperm production with anatomic factors and the release of sperm at ejaculation. Although many men are reluctant to be tested, this fear is often quickly eased when the results are known. No test has a better predictive capacity that a semen analysis performed by a reliable laboratory experienced in semen testing.

Sperm count, motility, and morphology are the big three in analysis of semen. The chances of pregnancy fall as the number of abnormal factors in a semen increase from one to two and from two to three. Abnormalities in all three categories is (oligoasthenoteratospermia).

Concentration is expressed as the number of sperm in each milliliter of ejaculate. Often a semen analysis is read as abnormal because only total sperm count is considered rather than the count per ml. If there are no sperm, the condition is called azoospermia. Causes of azoospermia can be genetic factors, an obstruction and/or hormonal problems. To exclude retrograde ejaculation (passage of the sperm into the bladder instead of out the urethra) a second semen analysis with evaluation of urine sample after ejaculation should be performed. Endocrine testing should also be performed. Unless the cause is immediately obvious, genetic studies may be needed. If the count is under 20 million per ml, the individual is said to have oligospermia. It is not really a diagnosis, but a finding, and virtually every source of male infertility has the finding of oligospermia. It shows the likelihood of pregnancy, not what is wrong.

Motility (movement of the sperm) is very seldom above about 80%. Samples under 10% should be scrutinized for lab or collection errors. Labs differ in what they consider normal motility. Normal ranges are probably about 40-70%. Be aware of the sample that looks too good on paper. Problems with motility are referred to as asthenospermia.

Morphology refers to the shape of the sperm. There are two different classification systems in use. According to the traditional World Health Organization classification, normal forms should be over 30%. Using a more refined classification including the “strict” criteria developed by Kruger, fertilization after IVF was 37-47% when there are less than 14% normal forms and 85-88% when there are over 14% normal forms.

The most useful parameter in evaluation of a semen sample is total motile sperm. Too often a sample is judged good or poor by looking at only one of the above parameters. The correct formula for use to judge a sample is Total motile = (Volume of sample) X (Concentration of sperm) X (motility).

Standard recommendation is that semen samples should be analyzed after 3-4 days of abstinence in order to have the maximum chance of a satisfactory evaluation. In reality, it may be more appropriate to produce a sample at your natural intercourse interval. Regardless, it is most important that the days of abstinence be recorded. If there is a good sample after twelve hours of abstinence—that’s real good. Semen quality among men of proven fertility can vary considerably between samples. Withdrawal sex should not be used for producing a sample for analysis. The best sperm may be lost in the first several drops of semen. Artificial lubricants may lower motility and viability. If successful masturbation is not possible, many fertility clinics have condoms especially designed for this purpose.

Be aware of the laboratory that is performing the semen analysis. Hospital labs are notorious for letting the sample sit too long before analysis, and too often technicians interpret semen samples with little formal training in semenology. The quality of the semen may be much better than reported. Often when white blood cells (WBC’s) are reported, these are actually immature sperm cells. The distinction between WBC’s and immature sperm can save unnecessary treatment with antibiotics. The results of the semen analysis may also overestimate sperm quality, but generally a sample reported as too good is much less worrisome for everyone.

If a repeat semen analysis is also low, the next step is hormone testing. The basic evaluation includes blood tests for luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone. If there has not been a recent evaluation, prostate specific antigen, comprehensive metabolic panel and complete may be included. If FSH levels are high, there is reduction in sperm production, while low FSH and LH indicates a “stress” pattern or communication problem within the endocrine system. Normal levels may be seen with obstruction of the sperm ducts. This is only a basic guide and there is considerable variation. The advisability of more extensive testing of sperm and sperm function, such as sperm penetration assays, antibody testing, and sperm viability studies should be highly questioned on a cost benefit basis. These tests may be valuable experimental tools, but truly offer very little to alter course of therapy and are best performed and read only by highly specialized clinics. Urologists, while very capable of a thorough exam and can exclude significant pathology, unfortunately are often are not particularly interested or trained in complete evaluation and treatment of the infertile male. If sperm counts are less than 10 million total motile sperm, a relatively quick referral to a fertility center is probably the most productive route. Hopefully, their team includes an andrologist and reproductive urologist. At 10-20 million total motile IUI should be considered.

Therapy for male infertility

Lifestyle There is a clear relationship between male obesity and decreased testosterone and decreased libido. Smoking has been clearly linked with decrease in sperm function. This relationship is very clear and very real. Additionally, smoking frequently leads to difficulty in establishing an erection in men over 40. Caffeine has the effect of temporarily exciting sperm, but then they don’t live as long. It is unclear if the occasional alcoholic beverage affects sperm counts or function, but chronic and heavy use is clearly dangerous.. Running over 20 miles a week can reduce fertility. Long hot baths/ sauna may be detrimental. There is no evidence that changing form briefs to boxers improves fertility

Medical A survey of any medications used is important. For example, calcium channel blockers, which are excellent drugs for hypertension, have also been shown to block fertilization. The fashion for clomiphene use waxes and wanes. It is sometimes prescribed more because of the lack of alternatives. It has not been conclusively shown to increased fertility and its use should have a precise indication. Viagra™ does not improve libido , but it can enhance sexual performance. There is no evidence of adverse effect on sperm.

Surgical A varicocele is a varicose vein of the scrotum. It has been theorized that this dilation of the veins increases scrotal temperature and reduces semen quality. There are some very positive scientific reports on improvement in sperm after the veins have been closed (ligated, occluded) or removed. Sperm counts may rise somewhat after surgery, but the hard evidence is completely lacking in relation to varicocele repair having any positive effect on fertility. If a surgeon finds a varicocele, there is a good a chance the opportunity to “have it fixed” will be offered. Value for testicular biopsy except in conjunction with cryopreservation of sperm is questionable.

Intrauterine insemination (IUI) IUI is the removal of sperm from the semen during a "sperm prep" and placement of the "washed" sperm into the uterus. Although artificial insemination (AI) has been performed for a very, very long time, it was not until the techniques of sperm preparation were refined from IVF technology that IUI became widely used. It has now replaced other types of insemination procedures such as intracervical and vaginal.

To begin the process of IUI, the seminal fluid is removed from the sperm, "sperm prep" is sperm "washing". To do this semen is mixed with a commercially available medium and placed in a centrifuge. The fluid is taken from the top of the tube and discarded and the of sperm pellet is again mixed with medium for a second centrifugation. The fluid is again removed and the remaining pellet is suspended in a small drop of medium inserted through the cervix into mid uterine cavity.

IUI is used in cases of male factor infertility to improve the number of sperm reaching the site of fertilization. IUI may by-pass the cervix, which is the main site of female sperm antibody production. It may also aid in bypassing tight cervix whether of constitutional or post surgical origin. When used in conjunction with ovulation induction drugs, IUI is estimated IUI increase chance of pregnancy by about 3 percent. Some have advocated several cycles of IUI as therapy for unexplained infertility. IUI may also be used in conjunction with fertility promoting agents in order to increase their effectiveness. In our clinic we commonly use IUI as routine semen testing rather than discarding the semen sample after it has been analyzed. An ultrasound scan before the insemination allows evaluation follicle and endometrial development. At the time of the insemination the amount and quality of cervical mucus is recorded. Most pregnancies are achieved with in the first 3 cycles if ovulation is occurring. IUI is an effective therapy and useful adjuvant, but many expect more from the procedure than it can offer.

During the sperm washing, the sperm are activated so that capacity to fertilize is immediate. Unfortunately, it also means that their life span is limited, so timing is critical. The natural reservoir of sperm in the cervix has been bypassed so the sperm don’t have the same lasting power. Semen cannot be placed directly into the uterus without the risk of severe contractions. This is due to the high levels of prostaglandins present and is a reason why the sperm must be washed prior to IUI. There is usually no, or minimal cramping with IUI. Severe pain and especially fever should be reported.

Intracytoplasmic sperm injection (ICSI) was introduced in 1992, and it is possibly the most important advance in the treatment of infertility since IVF. With sperm aspiration directly from the testis when necessary, ICSI can correct a majority of male infertility, regardless of cause. ICSI is a technique whereby a single sperm is directly injected into an egg bypassing the outer coverings of the egg and thus, some of the barriers to fertilization. Since a very small number of sperm are needed for this procedure, it has a very important advantage for men with extremely low sperm counts or sperm motility.

When there are more than 20 million total motile sperm, the chances of fertility are good. When in vitro fertilization (IVF) is used, there is little difference in fertilization rates with samples above 5 million. Every fertility specialist has been surprised with a pregnancy that occurred with counts so low as to border on sterility. In the past, the prognosis for men with very low sperm counts was very poor and often donor sperm became the most viable option for achieving pregnancy in the wife. We can not absolutely predict the limits of male fertility and it truly may take only one good sperm. It may mean assisted reproduction, but virtually all male factor infertility is now treatable with relatively good success.

An egg = ovulation

For the female, ovulation represents a culmination of a precise sequence of hormonal events. Failure to ovulate is the most common cause of female infertility. The only truly sensitive test for ovulation is. No test for ovulation short of establishment of a pregnancy is very sensitive. The larger the number of subjective and objective findings that suggest ovulation, the more likely that ovulation has occurred.

Women with regular cycles are not always ovulatory and women with very irregular cycles are not always infertile. Ovulation occurs with the greatest frequency in cycles that are between 26 and 32 days apart. Pelvic pain at midcycle associated with ovulation (mittleschmerz) is often associated with ovulation, but is not felt in a high percentage of women. Typically, this pain will alternate right and left, but some women either ovulate on one side or will have pain on one side despite alternating ovulation right and left. Under the influence of increasing estrogen as the follicle grows, there is an increase in cervical mucus production. The mucus will achieve an egg white consistency near ovulation. This mucus is a good sign and is conducive to sperm survival. In the past, post-coital tests (PCT) have been used to evaluate the quality of the cervical mucus and presence and motility sperm. A predictive value of the PCT was not shown in several clinical trials. The basal body temperature (BBT) while a nuisance, is cheap, reasonably easy and reliable. The temperature will usually be less than 98 degrees before ovulation increasing by about one half degree after ovulation. If this shift which should occur around day thirteen or fourteen occurs, the temperature chart is said to be biphasic. The temperature chart will have little value and should not be used in individuals with cycles under 25 or over 35 days. BBT tracking for over several months adds little to the infertility investigation. Ovulation predictor kits (OPK) and monitors measure luteinizing hormones (LH). The presence of a LH surge does not necessarily indicate ovulation has occurred. OPKs are universally difficult to interpret, and no one brand has been shown superior. The ovulation monitors have additional benefits for Fertility drugs, specifically clomiphene, often cause falsely positive color change using the predictor kits. Often patients with ovarian dysfunction, specifically PCOS, will have chronically elevated levels of LH and the test kit may be constantly or erratically positive. The benefits of the above tests are that each is simple, easy and relatively inexpensive. Additional techniques used under the guidance of physicians may include mid-luteal progesterone determinations drawn as a blood sample about seven days after ovulation. Some pregnancies are achieved even though the progesterone level is low. Progesterone is secreted in pulses that may reduce the effectiveness of this test. Ultrasound is an excellent method to follow follicular development and monitor effectiveness of fertility drugs. Most often, ovulation itself is not documented, but only that a preovulatory follicle existed at the appropriate time. The expense of ultrasound limits its use to probably no more than one or two times per month except for gonadotropin stimulation monitoring. The endometrial biopsy has been frequently used in the past to determine ovulation and exclude luteal phase defect. This technique should be considered outmoded, as it is too expensive, too imprecise, and too painful for routine use.

Over age 35

Advances in medical care systems and changes in demographics have changed our concept of “old” and “young.” Some women have delayed childbearing while other life goals are being met; others are in new relationships at later ages, while others may be at the end of a very long path of unsuccessful fertility therapy. It seems everyone has a family member or friend of a friend who had a pregnancy after age 45, but pregnancy after age 42 becomes increasingly rare. Numerous studies show that the average age that the last child is born is age 41. Regardless, the many women are kept awake at night by the ticking of their biologic clock.

The steady decline of eggs since before birth becomes more pronounced after age 30 and rapidly accelerates as age 40 nears. Any factor that results in the destruction of oocytes such as surgery, radiation, pelvic disease or genetic disorders serves to hasten the loss.

An essential part of the evaluation of all women over 35 is measurement follicle stimulating hormone (FSH) performed on day 2-3 of the cycle. Pregnancies are seldom achieved in women with FSH levels over 20 IU/l. Levels above 10 are very worrisome and many with levels above 8 will have decreased responsiveness to ovarian stimulation. Fertility agents work by increasing FSH and are likely to be ineffective when levels are already high. FSH levels are determined in conjunction with a blood level of estradiol that adds to the integrity of the test. Estradiol levels should be below 50 pg/ml for the FSH test to be valid. Use of a clomiphene challenge test to stimulate FSH has been reported to further increase the sensitivity. Here FSH and estradiol is are measured on cycle day 2-4 and 100 mg of clomiphene given. A repeat FSH is obtained on day 10 and should be below 20. While possibly more sensitive than FSH levels alone, the utility of the test has been questioned. Inhibin, which is produced from the follicle, has also been suggested as a marker of ovarian reserve, but its expense and lack of availability limit its use.

Anovulatory Infertility

A very high percentage of female infertility patients have ovarian dysfunction that is a sole or contributing cause of their infertility. The Most common cause of ovulatory defects falls along the spectrum of polycystic ovary syndrome (PCOS). PCOS and its differential diagnosis is presented in the PCOS material included elsewhere. In PCOS patients with insulin resistance, obesity and/or a family history of diabetes, a trial of metformin (Glucophage) in order before moving to the conventional fertility drugs.

Oral agents

Clomiphene citrate (CC) is considered the first line of therapy in anovulatory patients with normal TSH and prolactin levels. In comparison to the injectable medications, CC is quite safe, inexpensive, easy to use, and offers a chance of pregnancy in the initial month of use. CC is not a hormone, but a synthetic anti-estrogen. As such, binds to estrogen receptors in the brain and pituitary and “fools” the body’s regulatory mechanisms into perceiving that more estrogen is needed. This challenge is met by increased gonadotropin release (FSH and LH). However, CC is a double-edged sword also extending its ant-estrogenic effects to other sites that have estrogen receptors, specifically the endometrium and cervix. CC retards endometrial development and may decrease the possibility of implantation of the embryo. CC also markedly decreases the amount and quality of cervical mucus, which may impede sperm transport. Some investigators have proposed a detrimental effect of CC on the follicle, egg, or embryo, but this is much less well substantiated. It is clear that ovulation rate on CC exceeds the pregnancy rate.

In the past it was thought that clomiphene should only be used in patients that have clearly shown to not ovulate. Due to ease and safety its indications for use have generally been expanded to include trial in virtually all infertile patients. It is not because it is such a good drug, but because it is not a bad drug that is commonly prescribed. Often there can be subtle abnormalities of endocrine function that clomiphene may correct. The biggest mistake in CC therapy is that of its extended use. Virtually every patient will achieve a pregnancy on CC will do so within the first six cycles of use and the majority in the first three. Dosages range between 50 (one tablet) and 150 (three tablets) daily. Except in unusual circumstances, the dosage should not exceed 150 mg. daily. The risk of multiple pregnancies (very seldom over twins) is considered to be 5 to 10%. Side effects including hot flashes, mood alteration and cyst formation are relatively common. Empiric addition of thyroid supplement, prolactin inhibitors or corticosteroids should be used only when specifically indicated. Use of hCG to promote ovulation ins clomiphene cycles is used frequently, but there is little scientific support for its utility.

Some clinics are now using the aromatase inhibitor, letrozole, indicated for treatment of breast cancer, as an alternative to clomiphene. Early studies indicate that it may be equally effective while avoiding the detrimental effects of CC. Confirmatory studies are necessary before universal recommendations can be made.

Injectable agents

By convention, if oral agents not successful and if there is at least one open tube, the next step is to move to injectable fertility drugs, gonadotropin therapy. There are three problems with their use. There are 3 disadvantages of gonadotropin injection. 1) Gonadotropins are given by injection and most people do not like shots. 2) Gonadotropin injections are expensive. The cost of the medication alone runs from several hundred to several thousand dollars per cycle. Insurance companies vary in their willingness to cover the charges, which are usually from $500 to $3000 for the medications alone, with an additional $500-$1500 for labs and monitoring. Perhaps, the greatest limitation to their use is 3) the significant risk of multiple pregnancies.

The difference between giving too much and too little of these drugs is sometimes very small. The threshold, a point below which stimulation will be ineffective can be either low or high, while the therapeutic window, the difference between over and under response can be very narrow. It is difficult to determine in advance what individual response will be, "hyporesponder" or "hyperresponder." Hypo-response means a poor chance of pregnancy, while hyperresponder may be translated into multiple gestation.

Many infertility patients initially think of the possibility of twins, even triplets as exciting. This is just not an issue of having one’s hands full and one’s pocketbook emptying after the babies are born! Multi-fetal pregnancies carry high physical risks for both mothers and babies. Especially in the European clinics where insurance covers the cost of IVF, gonadotropin stimulation has largely been replace with IVF allowing a limited number of embryos to be transferred, no more than two in women under age 35.

The Passageways (tubes)

If ovulation is occurring and the sperm parameters are normal there is an increased possibility of tubal damage. The may come for internal tubal obstruction or external adhesive disease that preventing normal tubal function.

Pelvic scarring as a result of pelvic inflammatory disease (PID) after infection is common. The pelvic infection may have been severe requiring hospitalization or may have been so mild that it is mistaken for abdominal flu, urinary tract infection, or other transient problems. The tubes can be completely blocked and not amendable to reconstruction. If hydrosalpinges are found, the most optimistic chance for pregnancy is about 30%. It has been s conclusively shown that hydrosalpinx significantly reduces success with IVF and it is suggested that involved tube be surgically closed or removed. Milder cases of pelvic adhesions can be treated by surgical procedures to improve the movement of the tube and the ability of the tube to collect the egg from the ovary at ovulation.

A common cause of pelvic disease is endometriosis. The amount of pelvic pain is not related to stage of endometriosis and degree of pelvis scarring.. Some sever e cases have little pain. It is thought that at least 30% of infertile women have some degree of endometriosis. In its milder forms, it may be more of a symptom than a cause of infertility. There are a number of modalities for treatment of endometriosis including medical and surgical approaches.

The Uterus

Of the above compartments, the uterus is the least likely to be the direct cause of infertility. Abnormalities of the uterus associated with infertility include: 1)Uterine fibroid(s) (myoma or leiomyoma), 2) Endometrial polyps, 3) Intrauterine adhesions (Asherman Syndrome), and 4) Congenital anomalies

The relationship between uterine fibroids and infertility is based on both size and position. Fibroids located well away from the endometrial cavity are less likely to be important than submucosal fibroids, Fibroids under 30 mm are less likely to cause infertility. Myomectomy, although invasive procedure are successful procedures, although it increases the risk of uterine rupture during in the later stages of pregnancy and labor. Polyps less than 10 mm are not thought to be a cause of infertility. Asherman syndrome is caused by the destruction of the basal layer of progenitor endometrial cells. Although relatively uncommon it can arise form pelvis infection or after dilation and curettage. Congenital uterine anomalies, especially uterine septa, as a cause of recurrent pregnancy loss is well substantiated, but an association with infertile is debated.

Evaluation of Pelvic anatomy

There are three major ways to evaluate pelvic anatomy: ultrasound scan, hysterosalpingogram, and laparoscopy/hysteroscopy.

Ultrasound is an indispensable part of infertility evaluation and monitoring of therapy. Ultrasound should be performed before any more invasive anatomic evaluation. With ultrasound the ovaries can be evaluated in search of PCOS indicated by >12 small cysts and/or increased ovarian volume, ovarian compromise indicated to small volume, ovarian cysts, and endometriomas. Hydrosalpinges are often seen on ultrasound. Ultrasound is also gives an excellent view of uterine architecture in search of fibroids, polyps, and endometrial overgrowth. It is also invaluable in determining follicle growth and endometrial response. Ultrasound scan should be performed by individuals in reproductive physiology, not just pathology. The convention hospital ultrasound scan while exclude serious pathology may fails to report the subtleties necessary in an infertility investigation.

The sensitivity of ultrasound in detection abnormalities of the uterine cavity can be increase considerably by sonohysterography (sonoHSG) where about 10 cc of sterile water or saline is by instilled through a catheter placed into the cervix while viewing the uterus with transvaginal ultrasound.

The hysterosalpingogram (HSG) is a screening test performed in a hospital x-ray department in order to evaluate the contour of the uterine cavity and to determine if the tubes are patent (open). During an HSG, liquid dye is passed through an instrument placed in the cervix. Passage of the dye and outline of the uterus and tubes can easily be visualized by a special x-ray technique called fluoroscopy. Some women conceive after an HSG without additional therapy. This is thought to be due to a “flushing out” effect on the tubes and the removal of small bits of scar tissue. HSG is an excellent method to evaluate the possibility of some congenital abnormalities of the uterus, but its overall usefulness may be limited. About one in three cases will give a false HSG reading, either false positive or false negative.

If the HSG is abnormal, a laparoscopy and/or hysteroscopy is needed for confirmation and treatment. If the test is negative and nothing has been found, the results can’t be trusted and a laparoscopy or hysteroscopy may be necessary to exclude a problem. It is also common for the tube to have a muscle spasm during the procedure and appear blocked. The ability of the tubes to be freely mobile is very important. The tubes may be open, but scarring (adhesions) may prevent the tubes from capturing the egg at ovulation. Open tubes do not equal normal tubes. Perhaps, finding the tubes open may be sufficient to progress to a more aggressive ovulation induction. A personal opinion is that as a screening test, HSG is too painful, too costly, and just isn’t good enough.

Laparoscopy and hysteroscopy represent the definitive method to evaluate pelvic anatomy. Most often the procedure is performed in an outpatient surgical facility with recovery times is limited to 1-3 days. Specific reasons to consider laparoscopy include: 1)pelvic pain to exclude adhesions and endometriosis, 2) known endometriosis to evaluate progression to the disease, 3) Obvious abnormalities on ultrasound scan 4) Suspected previous pelvic infection or pelvic inflammatory disease (PID) 5) Previous pelvic or abdominal surgery 6) No other cause has been found - normal semen and ovulatory parameters Before proceeding to injectable fertility drugs, or IVF

It is recommended that a hysteroscopy be performed at the same time at laparoscopy. Most laparoscopic surgeons now begin the procedure with the thought that if the problem is found, it is corrected at that time. The exclude removal or closure of a damaged tube. Ovaries should be conserved if at all possible. Still it is preferable that if the laparoscopic surgeon does not feel comfortable in the needed surgery, that the procedure be stopped and the patient referred to a specialist. A benefit of laparoscopy is that practically any fertility problem that can be seen by laparoscopy can also be treated by laparoscopy. A surgeon who has experience in correction of the problems related to infertility should be chosen. There is no use to look but not correct a problem. However, it is better to look and discuss rather than incompletely or incorrectly treat.

Assisted Reproductive Technologies (IVF)

In vitro, literally meaning “in glass,” refers to a natural process that is performed outside the body. It is from this literal translation that the term “test tube baby” arises. In vitro fertilization and embryo transfer (IVF-ET) represents the flagship of assisted reproduction. It is from IVF-ET that other technologies draw their impetus and scientific foundation. The American Society for Reproductive Medicine states, “in vitro fertilization for infertility, not solvable by other means, is considered ethical.” For some, assisted reproduction may represent the last hope at the end of a long path of infertility therapy. For others, it may be the best place to start, depending on age and cause of infertility. IVF is being used increasingly for treatment of PCOS. The major factor limiting its greater use is its high cost.

IVF offers several distinct advantages that make it more cost-effective than it might seem initially. Perhaps the largest benefit, a desire shared by both clinician and patient, is to evaluate the capacity of the oocyte to be fertilized. An additional advantage is that a more aggressive approach can be taken toward ovarian stimulation. Not only does this decrease the chance of multiple pregnancies, it reduces the risk of more pronounced cystic change.

Stages of an Infertility Investigation

Infertility investigations and therapy can be described in four stages. The speed at which the investigation proceeds is variable and related to each couple. In some cases when a diagnosis is already known, therapy may start at one of the more advanced stages.

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