• Introduction
  • Classification of infertility
  • Diagnosis
  • Treatment
  • Ethical Issues
  • Infertility Evaluation
  • Laparoscopy
  • Microlaproscopy
  • Hysterosalpingogram
  • Male factor
  • male Infertility --- Overview
  • The Hypothalamic-Pituitary-Gonadal Axis
  • Leydig Cells
  • Seminiferous Tubules
  • Hormonal Control of Spermatogenesis
  • Transport-Maturation-Storage of Sperm

    • Introduction
      Human beings are remarkably fertile. Most females are capable of conceiving and bearing children beginning in their mid-teen years. While women in industrialized societies usually bear children in their 20s and 30s, women can give birth well into their 40s and beyond. Men can be fertile into extreme old age. Unlike most mammals, humans can mate successfully year round; fertility is not restricted to a particular season of the year or to brief episodes of female heat.

      But the process of reproduction is immensely complex. For conception to take place and pregnancy to begin, hundreds of individual hormonal, chemical, and physical events must take place in a precise order. For example, a sperm must form in the testicle, mature in the epididymis, be released into the female vagina, "swim" through the cervical opening, continue through the uterus and into a fallopian tube. In the tube, it must encounter a viable egg within 12 hours or so of its monthly release, attach itself to the egg, penetrate its outer vestments and fertilize the ovum within. After staying in the fallopian tube for about two days, the fertilized egg must descend into the uterus, grow and divide for a few more days, and then implant itself on the uterine wall.

      A single disruption, small or large, in any of these events and conditions can cause infertility. The sperm may not be viable it may be dead, it may contain the wrong number of chromosomes, it may have been stored too long after its formation. Or it may be viable but immotile, meaning that it cannot "swim" correctly. It may be perfectly healthy but not accompanied by enough other sperm, for although only one sperm is ultimately required for fertilization, men whose semen contains less that 20 million sperm per milliliter frequently have infertility problems. The sperm ducts may be blocked, because of past infection or injury. The man may not be able to ejaculate, or his ejaculation may propel the sperm backward into his bladder rather than out through the penis. Once inside the cervix, the sperm may meet mechanical or chemical roadblocks. A muscle spasm may eject the sperm, the cervical mucus may be too thick to penetrate, or chemically hostile to the sperm. The fallopian tube may be blocked by scar tissue. If the sperm does manage to reach the egg, it may not be able to penetrate its defenses to fertilize it. A fertilized egg may become stuck in the fallopian tube. Or it may not be able to implant successfully in the uterus.

      In the late 20th century, medical science has made great advances in understanding each stage of the reproductive process and in identifying the problems that can occur at each step. In an increasing number of cases these barriers can be corrected or worked around in order to achieve fertility for about 65% of couples who seek the help of fertility specialists.

      Is infertility becoming more common? Despite public worry and discussion, the actual incidence of infertility has remained fairly stable over the years. Infertility grows more common with increasing age; about 33% of couples in their late 30s are infertile. The age factor has taken on new importance as many people have put off marriage and children until certain educational or career goals are reached.
      Classification of infertility

      • Primary infertility if there was no previous pregnancy
        (approximately 40% of infertile couples).
      • Secondary infertility if there was a previous pregnancy whatever the outcome
        (approximately 60% of infertile couples).
      • Natural conception depends on satisfactory ovulation, transport of viable sperm and egg
       into the female reproductive system. Hormonal control, timing and frequency of
       intercourse as well as the general health status of the couple influence natural conception.
       Infertility affects one in seven couples and affects both men and women. The most
       important factor affecting a couple’s fertility is the woman’s age. For women aged 25 or
       under, 60% achieve conception within 6 months and 85% at one year. However, if the
       woman is aged 35 years or older, the conception rates are less than half. Male fertility
       also declines with age.
      • It is important to remember that the majority of infertile couples can achieve a pregnancy
        and live birth with treatment, they are sub fertile. Only minorities of patients are sterile, i.e.
        even with treatment they would be unable to conceive. This could be due to no sperm,
        absent or non-functioning ovaries or an absent uterus (womb).

      Even the most fertile human couple does not necessarily conceive the first time sexual intercourse takes place. In fact, the chance of conception in any given month among fertile couples attempting to conceive is about 20%, or one chance in five. To avoid unnecessary testing and treatment, most doctors will not make the diagnosis of infertility until one year of unprotected intercourse has failed to result in pregnancy. Some cases, involving older couples may be diagnosed sooner and treated more aggressively.
      Once the diagnosis is made, examinations, testing and history-taking begin to find the cause(s) of infertility. In about 30% of infertility cases, the problem can be found solely in a medical problem of the woman's; in another 30%, male factors alone cause the infertility; and in another 30% of cases, both partners have conditions which render the couple infertile. In the remaining 10% of cases, no clear cause can be found.
      Women are given a physical and pelvic examination, laboratory tests, and one or more imaging procedures to locate the problem which may be causing infertility. Testing may include exploratory surgery, using laparoscopy. In this technique, a small fiber-optic tool is inserted through a "keyhole" incision to allow the physician to inspect the reproductive system. Advanced ultrasound imaging may also reveal structural or functional problems. One commonly found condition during the infertility evaluation is endometriosis. In this disorder, cells from the endometrium, which normally line the uterus, spread in patches and cysts throughout the female reproductive system. Additionally, some women do not ovulate regularly or at all. Others may produce eggs regularly that are prevented from being fertilized, descending or implanting.
      Men are tested for the presence, quantity and quality of their sperm. The most common problem affecting male sperm levels is a varicocele, a tangle of veins surrounding the testicle. Surgical correction of large varicoceles restores fertility in about two-thirds of cases. Other causes of male infertility include insufficient hormone levels (which may be supplemented); blocked tubes which carry sperm (which can sometimes be surgically repaired or bypassed), untreated diabetes or prostate disease and other conditions.
      After testing is complete; doctors devise a strategy for each couple to increase fertility. The optimum treatment is one that allows existing natural processes to take place. Sometimes, very small adjustments in intercourse frequency and timing may result in pregnancy. Patients are taught to identify the woman's most fertile times so that intercourse can take place. Practices that temporarily result in lowered sperm counts or abnormally formed sperm, including the use of certain medications, alcohol, and hot tubs or saunas—can be curtailed.

      If the problem is insufficient sperm, centrifuging, chemical treatment, or other procedures to be more potent can concentrate a sperm sample. Following such adjustments, the sperm can be introduced into the woman's body. Lack of ovulation can be treated with hormones and chemicals to produce "superovulation," which can be followed by normal intercourse, artificial insemination or other ways to bring sperm and egg together.

      Once thought radical and futuristic but now considered quite routine, the best-known medical "fix" for infertility is in vitro fertilization. "In vitro" means "in glass," and it involves the mixing of sperm and egg in the laboratory, outside the human body. After fertilization takes place, the zygote (fertilized egg) may be surgically placed in the woman's fallopian tube. Alternatively, it may be allowed to develop further outside the body and then be introduced into the uterus in an effort to establish a pregnancy.

      One of the most recent developments in ART (Assisted Reproductive Technology) is Intracytoplasmic Sperm Injection, (ICSI). This microsurgical procedure involves injecting a single sperm into an egg, allowing men with extremely low sperm counts to become fathers. Further advances in ART are expected from the quickly evolving fields of genetics, imaging, and biotechnology.
      Ethical Issues
      The rapid development of new medical technology has raised many ethical and legal issues. Society is only beginning to devise acceptable answers. Philosophers and theologians ask whether humans have the right to tamper with natural processes.

      Practitioners and their patients have more immediate concerns—what shall be done with "extra" eggs, sperm, and zygotes? Must they be kept frozen indefinitely? At whose expense? Who "owns" them if the parents divorce or die?

      Another issue involves the identification and selection of "the best" sperm, egg or embryo. Many people wonder about the moral effect on our society of any attempt to prevent all children with defects from being born.

      When fertility treatment results in multiple pregnancies, couples face an ethical dilemma. While it is possible to selectively abort one or more embryos to improve the chances of the others survival and to reduce the burden on parents of raising quintuplets or sextuplets, this is a difficult decision for couples. Is this a justifiable act? Does this differ substantially form abortion as traditionally practiced?
      Infertility Evaluation
      If you are under the age of 35 and you and your partner have been trying to conceive for one year without success; or if you are over the age of 35 and have been unsuccessful after trying to conceive for six months, it is time to seek medical treatment for infertility.

      The first step in overcoming infertility is to perform what is called the infertility evaluation. We realize that most patients have limited resources to dedicate to building a family and our philosophy is to treat patients as quickly, effectively and inexpensively as possible…making the best use of all available resources. The main concern during the evaluation is to only conduct the tests that will give the physician clues to the cause of infertility and ultimately lead to the development of an effective treatment plan. There are a number of tests that have traditionally been run as part of the initial work up but may be unnecessary in many cases, such as the diagnostic laparoscopy, post coital test and endometrial biopsy.

      The results of the evaluation lead the physician to determine the cause of infertility which is most often related to age, ovulatory disorder, tubal factor or male factor.
      The first step for many couples seeking medical treatment for infertility is to discuss their inability to conceive with an OB/GYN. The OB/GYN will review the couple's medical history and conduct a complete physical on the female. The evaluation of the male's medical history includes a discussion of previous pregnancies, developmental problems, surgeries, testicular trauma or infections and environmental exposure. The female medical history includes review of previous pregnancies, painful periods or pelvic pain, infections and previous surgeries. The age of the patient must be taken into consideration when developing a cost-effective, medically appropriate evaluation and treatment plan. While there is little necessity to initiate aggressive therapy for a 20-year old with unexplained infertility, those over 35 deserve a more aggressive approach.

      Based on the results of the medical history evaluation and physical, the OB/GYN will often recommend that the couple see a reproductive endocrinologist for a routine infertility work-up to determine the cause of infertility. After the cause is determined, your physician will work with you to develop a personalized treatment plan that will help you build the family of your dreams.
      Each month, your endometrium, the lining of your uterus, grows thick with blood vessels, glands and stored nutrients around the time of ovulation to allow a fertilized egg to implant and grow. If no fertilization occurs, the thick lining sheds as menstrual flow. Two hormones, estrogen and progesterone, control the growth and stabilization of the endometrial tissue and if your body does not produce enough of these hormones your uterus may be unable to support a fertilized egg.

      An endometrial biopsy is a test performed to evaluate the endometrial tissue that lines the walls of the uterus to determine if your body is producing enough estrogen and progesterone. However, ovulation induction treatment, which is usually part of most fertility treatment plans, corrects this problem if present. As such, little information is actually gained from an endometrial biopsy. Newer tests such as integin vB3 or endometrial function not traditionally performed along with the endometrial biopsy may provide additional information regarding implantation.

      If the endometrial biopsy is performed, it should be done 11 to 13 days after a positive ovulation predictor test result. The physician will place a speculum inside your vagina, insert a small catheter through your cervix into your uterus and remove a small sample of your endometrial lining. The sample will then be sent to a pathologist who will examine your endometrial tissue under the microscope. The procedure only takes a few seconds but it may take up to one week to receive the results of the test. During the procedure, you may experience a pinch or slight cramping. You may have mild cramps following the procedure along with light bleeding and spotting.

      Hormonal studies measure the levels of certain hormones produced by your body during each menstrual cycle. Hormones affect every step necessary in achieving pregnancy from stimulating the development of an egg to ovulation and implantation of a fertilized egg in the uterus. If the hormones that affect fertility are not produced in specific amounts at specific times during your cycle, your chances of conceiving a child may be greatly inhibited.

      Your physician may run tests to determine the levels of the following hormones that play a role in ovulation and implantation of the egg:

      • Estradiol - stimulates the growth of the follicles and the production of cervical mucus from the cervix, and prepares the
         uterine lining for implantation of a fertilized egg.
      • Follicle stimulating hormone (FSH) - stimulates the development of the egg.
      • Luteinizing hormone (LH) - stimulates the release of the egg from the follicles.
      • Progesterone - stabilizes the uterine lining for implantation of a fertilized egg and supports early pregnancy
        The overproduction of the following hormones can negatively affect ovulation:

      • Androgens - normally small amounts of androgens (testosterone) are produced in women; excess production can interfere 
        with development of the follicles, ovulation and cervical mucus production.
      • Prolactin - stimulates milk production; prolactin levels may be higher than normal in certain disorders or when certain 
        medications are taken Thyroid - an underactive thyroid can result in high prolactin levels.
      • Thyroid Stimulating Hormone (TSH)- It stimulates the thyroid gland to secret certain amount of the thyroid hormones. Abnormal secretion in thyroid gland hormonal level may interfere with ovulation  

      Near the time you ovulate each month, estrogen production from the ovaries stimulates mucus production by your cervix. Sperm must penetrate and swim through this mucus, then travel through the reproductive tract to reach the egg for fertilization. In some cases, there is an incompatibility between the sperm and the cervical mucus, causing the sperm to become immobile or die, thus preventing fertilization. The postcoital test (PCT) evaluates the interaction between the sperm and your cervical mucus at a time near ovulation to determine if an incompatibility exists. Abnormal mucus may occur because of infections, surgery or clomid therapy. The PCT is a poor predictor of pregnancy success, but may be useful to determine the need for intrauterine insemination. If it is done too early before ovulation or too late after, the results may be falsely abnormal.
      In this section, details about the many potential causes of infertility including the most common diagnoses can be found - ovulatory dysfunction and male infertility. Most often, a diagnosis will be established after the infertility evaluation and workup. Once your diagnosis has been established, the physician will work closely with you to outline a treatment plan tailored to meet your specific needs.
      As a woman's age increases, her ability to become pregnant and carry a pregnancy to term decreases due to the many biological changes taking place in her body. From age 30 to 35, the chances of becoming pregnant gradually decline and after age 40 there is a sharp decline. Even if a woman becomes pregnant at a later age, chances of miscarriage and chromosomal abnormalities, resulting in birth defects such as Down's Syndrome, increase with age. Assisted reproductive technologies, including in vitro fertilization and intracytoplasmic sperm injection, also become less successful as age increases.

      Although it varies from woman to woman, fertility typically declines during your mid- to late-thirties. The number of your eggs declines, the likelihood of medical problems such as endometriosis increases, ovulation often becomes irregular, your ovaries produce less estrogen and progesterone and your eggs become resistant to fertilization and tend to have more chromosomal abnormalities.
      Ovulatory disorders are one of the leading causes of female infertility. The main factor in diagnosing an ovulatory disorder is medical history, though temperature charts, blood tests and ultrasounds are sometimes performed to confirm a diagnosis.

      Ovulatory dysfunction can manifest itself as the absence of menses (anovulation) or irregular, sometimes infrequent, menses. Anovulation is a condition in which eggs are not developed properly, or are not released from the egg sacs, or follicles, of the ovaries. Women who suffer from anovulation may not menstruate for several months or may continue to menstruate regularly even though they are not ovulating. The cause of anovulation is often unknown. However, in some cases the disorder can be traced back to an eating disorder, hormonal imbalance, excessive exercise, thyroid dysfunction, insulin resistance or other medical disorders.
      CERVICAL MUCUS TESTS: including a post-coital test (PCT) to see that sperm can penetrate and survive in the cervical mucus, and a bacterial screening. It is important to note that the appropriate time to do PCTs is just before ovulation when mucus is the most "fertile." PCTs at other times may give false results.

      ULTRASOUND EXAM(S): On the day of LH surge are used to assess the thickness of the endometrium (lining of the uterus), monitor follicle development and assess the condition of the uterus and ovaries. If the lining is thin, it indicates a hormonal problem. Fibroid tumors can often be detected via ultrasound, as well as abnormalities of the shape of the uterus and ovarian cysts. In some cases, endometriosis can also be detected. Many doctors order a second ultrasound two or three days after the first. This second ultrasound confirms that the follicle actually did release and can rule out lutenized unruptured follicle (LUF) syndrome---a situation in which eggs ripen but do not release from the follicle.

      HORMONE TESTS: if the blood test at your first appointment indicated a high LH to FSH ratio, an indication of polycystic ovarian disease (PCOD), your doctor will order an "Androgen Panel" to check levels of free testosterone and dihydroeprandrostone (DHEAS). Other tests tests that should be conducted on the day of LH surge include LH, FSH, Estradiol and Progesterone. Tests which can be done at any time (and therefore done at the second appointment) include: Prolactin, Thyroid Stimulating Hormone (TSH), Free T3, Free Thyroxine (T4), Total Testosterone, Free Testosterone, DHEAS and Androstenedione.
      The normal hormone levels for each of these during specific parts of your cycle are as follows:
      Lutenizing Hormone (LH)
      Follicular Phase (day two or three): <7miu/ml
      Day of LH Surge: >15mIU/ml
      Follicle Stimulating Hormone (FSH)
      Follicular Phase: <13miu/ml
      Day of LH Surge: >15 mIU/ml
      Day of LH Surge: >100 pg/ml
      Mid Luteal Phase (seven days after ovulation): >60 pg/ml
      Day of LH Surge: <1.5 ng/ml
      Mid Luteal Phase >15 ng/ml
      Prolactin: <25 ng/ml
      Thyroid Stimulating Hormone (TSH): 0.4 to 3.8 uIU/ml
      Free T3: 1.4 to 4.4 pg/ml
      Free Thyroxine (T4): 0.8 to 2.0 ng/dl
      Total Testosterone: 6.0 to 89 ng/dl
      Free Testosterone: 0.7 to 3.6 pg/ml
      DHEAS: 35 TO 430 UG/DL
      Androstenedione: 0.7 to 3.1 ng/ml
      <= less than;>= greater than; mIU=milli International Units; ml=milliliter; pg=picograms; ng=nanograms; uIU=micro International Units; dl=deciliter; ug=micrograms

      HYSTEROSALPINOGRAM (HSG): This test is used to examine a woman's uterus and fallopian tubes. It is essentially an x-ray procedure in which a radio-opaque dye is injected through the cervix into the uterus and fallopian tubes. This "dye" appears white on the x-ray, and allows the radiologist and your doctor to see if there are any abnormalities, such as an unusually shaped uterus, tumors, scar tissue or blockages in the fallopian tubes. If you are trying to get pregnant in the same cycle as an HSG, make sure to schedule the test PRIOR to ovulation so that there is no danger of "flushing out" a released egg or developing embryo.

      Although most women report only minor cramping and short-term discomfort during this procedure, some women, especially those who DO have blockages, report intense pain. Speak to your doctor about taking a pain medication about 30 minutes prior to the actual procedure.

      HYSTEROSCOPY: If a uterine abnormality is suspected after the HSG, your doctor may opt for this procedure, performed with a thin telescope mounted with a fiber optic light, called a hysteroscope. The hysteroscope is inserted through the cervix into the uterus and enables the doctor to see any uterine abnormalities or growths. "Photos" are taken for future reference. This procedure is usually performed in the early half of a woman's cycle so that the build-up of the endometrium does not obscure the doctor's view. However, if the doctor is planning to do an endometrial biopsy at the same time, it is done near the end of the cycle.

      LAPAROSCOPY: A narrow fiber optic telescope is inserted through a woman's abdomen to look at the uterus, fallopian tubes, and ovaries and to discern endometriosis or pelvic adhesions, and is the best diagnostic tool for evaluating the ovaries. This test is usually done two or three days before menstruation is expected, and only after an HCG beta blood test ensures the woman is not pregnant.

      ENDOMETRIAL BIOPSY: This procedure involves a scraping a small amount of tissue from the endometrium shortly before menstruation is due--- between 11 and 13 days from LH surge. It should ONLY be performed after an HCG blood test shows the woman is not pregnant. This test is used to determine if a woman has a luteal phase defect, a hormonal imbalance which prevents a woman from sustaining a pregnancy because not enough progesterone is produced.
      Ovulation assessment is an important part of every infertile couple's evaluation. A complete history and physical by your physician can often uncover obvious concerns. Although regular menstrual cycles suggest normal ovulation, that is not always the case. Normal ovulation is a complex process that requires many things to happen properly and at the correct time with the proper hormone levels. Often subtle hormonal imbalances or ovulation abnormalities result in "suboptimal fertility potential".

      There are a number of tools that enable us to evaluate both overt and subtle disturbances of ovulation. We employ these techniques in performing an initial menstrual cycle evaluation or to assess the effectiveness of prescribed treatment plans. Thus, ovulation testing and monitoring become important tools for both detecting ovulation problems and monitoring the effectiveness of treatment.

      A menstrual cycle evaluation may consist of many different components. You may need all or just some of the testing. This depends on which aspects of your ovulation we want to evaluate more closely. Thus, your cycle study will be personalized for your specific situation.

      Evaluating your ovarian function may require the following tests:

      • BBT's (basal body temperatures) 
      • Urinary LH testing 
      • Transvaginal pelvic ultrasounds 
      • Huhner's Test (post coital test) 
      • Endometrial biopsy 
      • Blood hormone testing (drawing blood to measure TSH & Prolactin. If you have excessive hairgrowth, obesity or acne we
        may add testosterone, DHEAS, 17-hydroxyprogesterone, fasting insulin and glucose, or dexamethasone suppression test).
      • Evaluation of ovarian reserve (either cycle day 3 FSH/Estradiol hormone testing or a clomiphene challenge test).
       You will be given specific information on each of the components that your physician has decided is needed to evaluate your
        ovulatory function. The results of these tests individually or in combination with other information will help your
        physician better determine the nature of your ovulatory function. The specific ovulation disorders that these tests are being 
        utilized to rule out include:

      1. Inadequate follicle growth patterns.
Each month (ovulation cycle) a follicle should develop and grow within one of the
         ovaries. This follicle is a small fluid filled cyst that contains the ovum (egg) destined to ovulate. It also produces the
         hormones estrogen and progesterone that ready the reproductive tract for conception and implantation. Disorders of
         follicular development can cause an inadequate follicular size or inadequate estrogen production which can interfere with
      2. Premature luteinization.
In response to a sharp rise in LH, the follicle ruptures and the egg is released. The collapsed follicle forms a corpus luteum and begins to produce progesterone to ready the uterine lining for implantation (attachment) of a fertilized egg.
         In patients with higher than normal serum LH levels, premature production of progesterone by the follicle may result in
         improper changes in the cervical mucus, tubal mobility, or endometrium (uterine lining). The elevated LH levels may also
         adversely effect egg quality. This problem is diagnosed by correlating follicle ultrasound results with hormonal testing.
      3. Luteinized unruptured follicle syndrome (LUF syndrome).
Follicle rupture and release of the egg should occur within 38
          hours of the urinary LH surge. Abnormal follicular development as well as pelvic adhesions can result in failure of  the ovary  to actually release the egg into the peritoneal (abdominal) cavity at the time of ovulation. This problem may be detected by correlating the follicle ultrasound results with urinary LH testing. HCG administration should correct this problem if it is due to a hormonal abnormality.
      4. Inadequate luteal phase.
The uterine lining, stimulated by estrogen and progesterone, prepares itself each month to accept
          implantation of a fertilized egg. This preparation requires an orderly growth of the lining. Hormonal imbalances can result in
          the development of a uterine lining that is out of phase with the fertilized egg. Thus, implantation or attachment of the egg to
          the uterine wall does not occur appropriately. This problem can cause infertility as well as recurrent miscarriages and is
          called an inadequate luteal phase. An endometrial biopsy timed 12-13 days after your LH surge is utilized to assess the
          uterine lining development.
      5. Diminished Ovarian Reserve.
With advancing age, egg quality and subsequently the chance of a normal pregnancy
          diminishes. The presence of normal, regular menses, does not necessarily mean you are releasing healthy eggs with each
          ovulation. This is most simply checked by measuring FSH and estradiol levels on the third day of the menstrual cycle.  Decreased number of antral follicle count on vaginal ultrasound may predict poor ovarian reserve.         
          If you should have any questions regarding the above information or the testing, please feel free to contact our office for
          further explanation. It is our wish that you fully understand the nature of the tests and why they are being performed.

      Endometriosis, a cause of female infertility, is a condition in which endometrial tissue, the tissue that lines the inside of the uterus, grows outside the uterus and attaches to other organs in the abdominal cavity such as the ovaries and fallopian tubes. Endometriosis is a progressive disease that tends to get worse over time and can reoccur after treatment. Symptoms include painful menstrual periods, abnormal menstrual bleeding and pain during or after sexual intercourse.

      The endometrial tissue outside your uterus responds to your menstrual cycle hormones the same way the tissue inside your uterus responds - it swells and thickens, then sheds to mark the beginning of the next cycle. The blood that is shed from the endometrial tissue in your abdominal cavity has no place to go, resulting in pools of blood causing an inflammation that forms scar tissue. The scar tissue can block the fallopian tubes or interfere with ovulation. Another result of endometriosis is the formation of ovarian cysts called endometrioma that may also interfere with ovulation.

      The cause of endometriosis is unknown though there are a few theories that suggest possible causes. One theory suggests that during menstruation, some of the menstrual tissue backs up through the fallopian tubes into the abdomen where it implants and grows. Another theory indicates that it is a genetic birth abnormality in which endometrial cells develop outside the uterus during fetal development.

      A laparoscopy, an outpatient surgical procedure, is necessary to confirm a diagnosis of endometriosis after a medical history review and pelvic exam. After the initial diagnosis, your physician will classify your condition as stage 1 (minimal), stage 2 (mild), stage 3 (moderate) or stage 4 (extensive) based on the amount of scarring and diseased tissue found. Based on the stage of endometriosis, your physician will determine the best treatment plan for you which may include medication or surgery, or a combination of both.
      Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, affecting an estimated five to ten million women of reproductive age. For women trying to conceive a child, PCOS is a serious, common cause of infertility - nearly half of all female factor infertility cases can be traced to PCOS. New medical insight into the disease has led to treatment options, including insulin-reducing ovulation medication (clomiphene, Metformin), dietary changes (low glycemic diet) and surgery (ovarian drilling), which have proven successful and allow many women to overcome PCOS and conceive a child naturally, while reducing the risk of miscarriage. Women who undergo treatment for PCOS but are still unable to conceive naturally often turn to assisted reproductive technologies, including IVF, and experience high pregnancy success rates.

      At  Noor our physicians specialize in this common, yet often misunderstood cause of infertility. We work closely with each patient to understand her specific medical case and personal goals, including weight loss, pregnancy or improving general health, and develop a holistic approach to reach those goals. Oftentimes, the road to overcoming PCOS is not an easy one and it takes a strong commitment from both the patient and the physician. The team at Noor is committed to supporting our patients every step of the way.
      Tubal disease, one of the many causes of female infertility, is a disorder in which the fallopian tubes are blocked or damaged. Your physician will review your medical history and do a complete pelvic exam to diagnose a tubal disorder. It is often necessary to undergo additional tests, including hysterosalpingogram and laparoscopy, to confirm the diagnosis.

      Scar tissue, infections and tubal ligation are often causes of tubal disease. Scar tissue resulting from endometriosis or abdominal or gynecological surgery, such as bowel surgery, cesarean section or a ruptured appendix, can block an egg from entering or traveling down the fallopian tube to meet the sperm, preventing fertilization. Infections, including chlamydia, can damage the cilia, the tiny hairs lining the fallopian tubes that help transport the egg, often preventing the sperm and egg from meeting. One result of damaged cilia is an ectopic pregnancy, which occurs when an egg is fertilized but, due to the damaged cilia, it is unable to travel to the uterus, growing instead in the wall of the fallopian tube. This condition can result in rupture, internal bleeding and further tubal damage. Many women who have undergone tubal ligation, had their "tubes tied", decide they want to have a baby at some point after the procedure.

      These patients most often undergo in vitro fertilization to bypass the blockage. In some rare cases, surgery can be done to reattach tubes after ligation.

      There are a number of treatment options available to overcome infertility caused by tubal disease. Successful treatment options include surgical removal of scar tissue, surgical repair of damaged tubes, tubal ligation reversal or in vitro fertilization. IVF typically provides the best results; however, surgical approaches may be advisable due to other pelvic findings such as hydrosalpinx or leiomyoma (fibroid).
      Laparoscopy is direct visualization of the peritoneal cavity, ovaries, outside of the tubes and uterus by using a laparoscopy. The laparoscopy is an instrument somewhat like a miniature telescope with a fiber optic system which brings light into the abdomen. It is about as big around as a fountain pen and twice as long.

      An instrument to move the uterus during surgery will be placed in the vagina. Carbon dioxide (CO2) is put into the abdomen through a special needle that is inserted just below the navel. This gas helps to separate the organs inside the abdominal cavity, making it easier for the physician to see the reproductive organs during laparoscopy. The gas is removed at the end of the procedure.
      Microlaparoscopy is the newest minimally invasive surgical technique that revolutionizes diagnostic laparoscopy. Just as rapid advances in electronics have shrunk computers to a fraction of their original size, similar advances in surgical instrumentation offer new opportunities to diagnose and treat surgical disease.

      While a standard laparoscope is about 10-12mm in size, (slightly less than 1/2 inch) recently developed microlaparoscopes are less than 3mm (slightly more than 1/10th of an inch). While previously small incisions were made inside the belly-button, now, certain surgical procedures can be performed with only a needle stick. I can place small scissors, graspers, biopsy instruments or a laser fiber through one or two additional 3mm needles. This enables me to perform diagnostic laparoscopy or simple surgical procedures using a local anesthetic and sedation through an intravenous catheter. This means much less incisional pain after your surgery. It also means less anesthetic, no sore throat, and less nausea. In many cases you may be able to resume all normal activities in just a few hours.

      frequently, laparoscopy is used to insure that the fallopian tubes are normal and there are no factors contributing to infertility. Unfortunately, sometimes I will find a problem that cannot be corrected with microlaparoscopy. If you have significant adhesions, endometriosis or other abnormalities, you will receive a general anesthetic and the operation is completed using standard laparoscopic techniques.

      Pain mapping is another useful microlaparoscopic technique. If you are suffering from chronic pain and previous surgical procedures have not localized the cause, a microlaparoscopic procedure may provide the answer. A microlaparoscopic diagnostic procedure is performed while you are sedated, but still awake. I will use a probe to gently touch various structures such as the uterosacral ligaments, the ovaries, tubes, uterus, bladder or an adhesion to see if that area duplicates your pain. If the source of your pain is located, surgery may be more effective at providing relief.
      Microlaparoscopy is in its infancy. Its' primary uses are for diagnostic surgery. But, as new instruments become available our capabilities will increase. I am very excited to offer my patients microlaparoscopy and truly believe this technique will simplify and reduce the cost of diagnosing the cause of pelvic pain and infertility.
      A hysterosalpingogram (HSG) is an X-ray of the uterus and fallopian tubes which allows visualization of the inside of the uterus and tubes. The picture will reveal any abnormalities of the uterus as well as tubal problems such as blockage and dilation (hydrosalpinx). If sterilization reversal is planned, the point at which the tubes are blocked can be seen. This helps to plan the reconstructive procedure.

      If the tubes are not blocked by scar tissue or adhesions, the dye will flow into the abdominal cavity. This is a good sign but it does not guarantee that the tubes will function normally. It does give a rough estimate of the quality of the tubal structure and the status of the tubal lining. Some cases where the tubes appear to be blocked where they join the uterus, may in fact be normal. Often blockage at this location may be due to spasm of the opening from the uterus into the tube or from accumulated debris and mucus blocking the opening. This can be managed by passing a very thin catheter into the fallopian tube either at the time of hysterosalpingogram or during a hysteroscopic procedure.

      A hysterosalpingogram may also indicate endometrial polyps, submucus fibroids, intrauterine adhesions (synechia), uterine and vaginal septa uterine cavity abnormalities, or the after-effect of genital tuberculosis. The hysterosalpingogram may or may not be able to detect pelvic adhesions, mild hydrosalpinx, small polyps, endometriosis, tubal phimosis (clubbing of the fimbria at the end of the tube), or immotility of the tube. Other tests, such as hysteroscopy saline sonohysterography or laparoscopy may be necessary to accurately evaluate your uterus.

      Although the purpose of the hysterosalpingogram is not therapeutic, sometimes forcing dye through the tube will dislodge any material which blocks it. A number of women have become pregnant following a hysterosalpingogram without further treatment.

      Generally there is no special preparation needed for this test. However, depending upon your diagnosis, you may need to take antibiotics to guard against possible infection. To ensure that you are not pregnant, the study is done between Day 7 and 10 of your cycle. Prior to the procedure you may take an anti-inflammatory medication. A small catheter is placed into the cervix and the dye is injected. You may feel heavy cramping during, and for several hours following this procedure. Expect a sticky vaginal discharge for a few days as the dye is expelled from the uterus. Use a pad or panty liner during this time to allow fluid to escape. Any dye that remains will be absorbed without any ill effect.
      Male factor
      Misconceptions are very common in the world of infertility. One popular myth is that infertility is the woman's problem and that once that "problem" is fixed, the couple will be able to conceive. This could not be farther from the truth. In fact, in nearly 30% of all infertility cases, the cause is attributed to a factor in the male and in an additional 30% of cases the cause is attributed to both male and female factors. Today, exciting advances in male infertility have introduced innovative therapeutic options that offer men, including those with no sperm in their ejaculate due to genetic conditions, a greatly improved chance to conceive their own biological offspring.

      At Noor , we understand that couples seeking treatment for infertility are in search of a program that will provide them with the best chance possible for conceiving a child. In order to maximize the chances for conception, we create a partnership with each couple to determine exactly what the goals are and establish a treatment plan to maximize all resources in an effort to reach those goals.
      male Infertility --- Overview
      Important issues related to the evaluation of the male factor include the most appropriate time for the male evaluation, the most efficient format for a comprehensive male exam, and definition of rationale and effective medical and surgical regimens in the treatment of these disorders. It is extremely important in the evaluation of infertility to consider the couple as a unit in evaluation and treatment and to proceed in a parallel investigative manner until a problem is uncovered. It has been shown that the longer a couple remains subfertile, the worse their chance for an effective cure. Many couples experience significant apprehension and anxiety after only a few months of failure to conceive. Unduly prolonged unprotected intercourse should not be advocated before a workup of the man is instituted. Initial screening of the man should be considered whenever the patient presents with the chief complaint of infertility. This initial evaluation should be rapid, non-invasive and cost effective. Of interest is the fact that pregnancy rates of up to 50% have been reported when only the woman has been investigated and treated even when the man was found to have moderately severe abnormalities of semen quality.
      The Hypothalamic-Pituitary-Gonadal Axis
      The hypothalamus is the integrative center of the reproductive axis and receives messages from both the central nervous system and the testes to regulate the production and secretion of gonadotropin releasing hormone (GnRH). Neurotransmitters and neuropeptides have both inhibitory and stipulatory influence on the hypothalamus. The hypothalamus releases GnRH in a pulsatile nature which appears to be essential for stimulating the production and release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH). Interestingly and paradoxically, after the initial stimulation of these gonadotropins, the exposure to constant GnRH results in inhibition of their release. LH and FSH are produced in the anterior pituitary and are secreted episodically in response to the pulsatile release of GnRH. LH and FSH both bind to specific receptors on the Leydig cells and Sertoli cells within the testis. Testosterone, the major secretory product of the testes, is a primary inhibitor of LH secretion in males. Testosterone may be metabolized in peripheral tissue to the potent androgen dihydrotestosterone or the potent estrogen estradiol. These androgens and estrogens act independently to modulate LH secretion. The mechanism of feedback control of FSH is regulated by a Sertoli cell product called inhibin. Decreases in spermatogenesis are accompanied by decreased production of inhibin and this reduction in negative feedback is associated with reciprocal elevation of FSH levels. Isolated increased levels of FSH constitute an important, sensitive marker of the state of the germinal epithelium.

      Prolactin also has a complex inter-relationship with the gonadotropins, LH and FSH. In males with hyperprolactinemia, the prolactin tends to inhibit the production of GnRH. Besides inhibiting LH secretion and testosterone production, elevated prolactin levels may have a direct effect on the central nervous system. In individuals with elevated prolactin levels who are given testosterone, libido and sexual function do not return to normal as long as the prolactin levels are elevated.
      Leydig Cells
      Testosterone is secreted episodically from the Leydig cells in response to LH pulses and has a diurnal pattern, with the peak level in the early morning and the trough level in the late afternoon or early evening. In the intact testis, LH receptors decrease or down-regulate after exogenous LH administration. Large doses of GnRH or its analogs can reduce the numbers of LH receptors and therefore inhibit LH secretion. This has been applied clinically to cause medical castration in men with prostate cancer. Estrogen inhibits some enzymes in the testosterone synthetic pathway and therefore directly effects testosterone production. There also appears to be an intratesticular ultra short loop feedback such that exogenous testosterone will override the effect of LH and inhibit testosterone production. In normal males, only 2% of testosterone is free or unbound. 44% is bound to testosterone-estradiol-binding globulin or TeBG, also called sex hormone-binding globulin. 54% of testosterone is bound to albumin and other proteins. These steroid-binding proteins modulate androgen action. TeBG has a higher affinity for testosterone than for estradiol, and changes in TeBG alter or amplify the hormonal milieu. TeBG levels are increased by estrogens, thyroid administration and cirrhosis of the liver and may be decreased by androgens, growth hormone and obesity. The biological actions of androgens are exerted on target organs that contain specific androgen receptor proteins. Testosterone leaves the circulation and enters the target cells where it is converted to the more potent androgen dihydrotestosterone by an enzyme 5-alpha-reductase. The major functions of androgens in target tissues include:

      1) regulation of gonadotropin secretion by the hypothalamic-pituitary axis.
      2) initiation and maintenance of spermatogenesis.
      3) differentiation of the internal and external male genital system during fetal development.
      4) promotion of sexual maturation at puberty.
      Seminiferous Tubules
      The seminiferous tubules contain all the germ cells at various stages of maturation and their supporting Sertoli cells. These account for 85-90% of the testicular volume. Sertoli cells are a fixed-population of non-dividing support cells. They rest on the basement membrane of the seminiferous tubules. They are linked by tight junctions. These tight junctions coupled with the close approximation of the myoid cells of the peritubular contractile cell layers serve to form the blood-testis barrier. This barrier provides a unique microenvironment that facilitates spermatogenesis and maintains these germ cells in an immunologically privileged location. This isolation is important because spermatozoa are produced during puberty, long after the period of self-recognition by the immune system. If these developing spermatozoa were not immunologically protected, they would be recognized as foreign and attacked by the body's immune system. Sertoli cells appear to be involved with the nourishment of developing germ cells as well as the phagocytosis of damaged cells. Spermatogonia and young spermatocytes are lower down in the basal compartment of the seminiferous tubule, whereas mature spermatocytes and spermatids are sequestered higher up in the adluminal compartment.

      The germinal cells or the spermatogenic cells are arranged in an orderly manner from the basement membrane up to the lumen. Spermatogonia lie directly on the basement membrane, and next in order, progressing up to the lumen, are found the primary spermatocytes, secondary spermatocytes and spermatids. There are felt to be 13 different germ cells representing different stages in the developmental process.

      Spermatogenesis is a complex process whereby primitive stem cells or spermatogonia, either divide to reproduce themselves for stem cell renewal or they divide to produce daughter cells that will later become spermatocytes. The spermatocytes eventually divide and give rise to mature cell lines that eventually give rise to spermatids. The spermatids then undergo a transformation into a spermatozoa. This transformation includes nuclear condensation, acrosome formation, loss of most of the cytoplasm, development of a tail and arrangement of the mitochondria into the middle piece of the sperm which basically becomes the engine room to power the tail. Groups of germ cells tend to develop and pass through spermatogenesis together. This sequence of developing germ cells is called a generation. These generations of germ cells are basically in the same stage of development. There are six stages of seminiferous epithelium development. The progression from stage one through stage six constitutes one cycle. In humans the duration of each cycle is approximately 16 days and 4.6 cycles are required for a mature sperm to develop from early spermatogonia. Therefore, the duration of the entire spermatogenic cycle in humans is 4.6 cycles times 16 days equals 74 days.
      Hormonal Control of Spermatogenesis
      Structural and functional relationship exists between the two separate compartments of the testis, i.e. the seminiferous tubule and the interstitium between the tubules. LH effects spermatogenesis indirectly in that it stimulates androgenous testosterone production. FSH targets Sertoli cells. Therefore, testosterone and PSH are the hormones that are directed at the seminiferous tubule epithelium. Androgen-binding protein which is a Sertoli cell product carries testosterone intracellularly and may serve as a testosterone reservoir within the seminiferous tubules in addition to transporting testosterone from the testis into the epididymal tubule. The physical proximity of the Leydig cells to the seminiferous tubules and the elaboration by the Sertoli cells of androgen-binding protein, cause a high level of testosterone to be maintained in the microenvironment of the developing spermatozoa. The hormonal requirements for initiation of spermatogenesis appear to be independent of the maintenance of spermatogenesis. For spermatogenesis to be maintained like for instance after a pituitary obliteration, only testosterone is required. However, if spermatogenesis is to be re-initiated after the germinal epithelium has been allowed to regress completely, then both FSH and testosterone are required.
      Transport-Maturation-Storage of Sperm
      Although the testis is responsible for sperm production, the epididymis is intimately involved with the maturation, storage and transport of spermatozoa. Testicular spermatozoa are non-motile and were felt to be incapable of fertilizing ova. Spermatozoa gain progressive motility and fertilizing ability after passing through the epididymis. The coiled seminiferous tubules terminate within the rete testis, which in turn coalesces to form the ductuli efferentes. These ductuli efferentes conduct testicular fluid and spermatozoa into the head of the epididymis. The epididymis consists of a fragile single convoluted tubule that is 5-6 meters in length. The epididymis is divided into the head, body, and tail. Although epididymal transport time varies with age and sexual activity, the estimated transit time of spermatozoa through the epididymis in healthy males is approximately four days.

      It is during the period of maturation in the head and body of the epididymis that the sperm develop the increased capacity for progressive motility and also acquire the ability to penetrate oocytes during fertilization. The epididymis also serves as a reservoir or storage area for sperm. It is estimated that the extragonadal sperm reservoir is 440 million spermatozoa and that more than 50% of these are located in the tail of the epididymis. The sperm that are stored in the tail of the epididymis enter the vas deferens which is a muscular duct 30-35 cm in length. The contents of the vas are propelled by peristaltic motion into the ejaculatory duct. Sperm are then transported to the outside of the male reproductive tract by emission and ejaculation.

      During emission, secretions from the seminal vesicles and prostate are deposited into the posterior urethra. Prior to ejaculation peristalsis of the vas deferens and bladder neck occur under sympathetic nervous control. During ejaculation, the bladder neck tightens and the external sphincter relaxes with the semen being propelled through the urethra via rhythmic contractions of the perineal and bulbourethral muscles. It is true that the first portion of the ejaculate contains a small volume of fluid from the vas deferens which is rich in sperm. The major volume of the seminal fluid comes from the seminal vesicles and secondarily the prostate. The seminal vesicles provide the nourishing substrate fructose as well as prostaglandins and coagulating substrates. A recognized function of the seminal plasma is its buffering effect on the acidic vaginal environment. The coagulum formed by the ejaculated semen liquefies within 20 to 30 minutes as a result of prostatic proteolytic enzymes. The prostate also adds zinc, phospholipids, spermine, and phosphatase to the seminal fluid. The first portion of the ejaculate characteristically contains most of the spermatozoa and most of the prostatic secretions, while the second portion is composed primarily of seminal vesicle secretions and fewer spermatozoa.