Infertility

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Infertility

Discussion || Causes || Treatments

Discussion

Infertility is all too common. Studies show that approximately 15% of American couples struggle with infertility. Approximately half of these patients seek treatment, and most significantly, about 85% of this group will conceive with the appropriate medical treatment.

Infertility is typically defined as a condition in which a healthy couple of childbearing age cannot conceive after more than a year of unprotected sexual intercourse. In women over 35 years of age, the time frame may be shortened to six months. Infertility categories are further subdivided into primary infertility - patients without any prior pregnancies, and secondary infertility - couples who are experiencing infertility after having had previous conceptions.

Infertility causes are varied and complex. During the normal fertility process, a sufficient number of normal sperm must be deposited in the vagina at the appropriate time during the menstrual cycle when sperm can penetrate the cervical mucus, ascend through the uterus and fallopian tubes, and fertilize the egg ( male factor infertility ).

The female must produce a healthy, mature egg that is released from the ovary. After release, the egg must travel down the fallopian tube so that the sperm may fertilize it. The fertilized egg then travels into the uterus and implants in the endometrium ( the uterine lining ), which will nourish the embryo's further development.

Infertility may be caused by disruption in any of these processes. Egg development and ovulation are under the control of complex hormonal interactions including FSH, LH, estradiol, progesterone, and others. Diseases of the thyroid, adrenal, pituitary, or hypothalamus glands can lead to ovulatory dysfunction. Certain conditions, such as polycystic ovarian syndrome, cause irregular or absent ovulation that leads to infertility.

Endometriosis

Blockage of the fallopian tubes can occur as a result of serious infection, congenital abnormalities, scarring from previous surgery, or endometriosis. Endometriosis is a major cause of infertility and may be present with no symptoms. Some studies indicate that endometriosis decreases pregnancy rates even though there may be little visible organ damage. Endometrial tissue attaches to organs, grows, divides, and can penetrate causing obstruction and other types of damage. Endometrial tissue is dependent upon estrogen for growth. The medications used to treat endometriosis lower estrogen levels, thus "starving" the aberrant tissue.

Multiple Causes

In many infertility cases, patients may experience more than one of the following conditions. Accordingly, a thorough evaluation of both partners is required. Research suggests that infertility cases fall into these categories:

Abnormal sperm parameters in as many as 30% - 45% of cases ( male infertility )
Ovulation and egg quality disorders in approximately 35% of cases
Pelvic adhesions
Endometriosis
Fallopian tube disorders
Uterine anomalies ( about 25% )
Combined male and female causes ( 10% )
Unexplained infertility - causative factors in 10% of infertile couples cannot be identified

Most infertility evaluation tests must be done at particular times during the menstrual cycle. Therefore, treatment is seldom initiated until the investigation is complete, for it is necessary to rule out all potential causes. For example, it does no good to treat the female with Clomid if there is an undiagnosed male factor infertility; in this case, the couple wastes months on ineffective therapy.

IVF or other advanced reproductive technologies are not always the treatments of first choice. Other less extensive treatments are often effective depending on the causal factors. A complete examination and diagnosis is crucial to determine the cause and timely medical treatment to insure a healthy pregnancy.

Some Causes

Cervical Factor

Once sperm are ejaculated into the vagina they must swim through the cervical mucus, pass the cervix, and enter the uterus. Their final destination is the end of the fallopian tube, where fertilization occurs. Sometimes there are abnormalities in the cervical mucus that can slow, damage, or destroy sperm. Some medications, notably Clomid, can cause a thickening of the mucus making sperm transport difficult.

It is possible that the female, or rarely the male, produces antibodies to the sperm. The body "mistakes" the sperm for invading pathogens and the immune system produces antibodies to destroy them. This is essentially the same reaction seen when the immune system identifies a foreign virus. The male may produce antibodies to his own sperm. There must have been "semen - blood" contact in the past for the body to produce these antibodies. This most often occurs as a result of testicular trauma.

A first line treatment for cervical factor may be intrauterine insemination ( IUI ). In IUI, specially prepared sperm are inserted directly into the uterus using a small catheter thus avoiding contact with the cervical mucus. If moderate male factor is present, or if there are other abnormalities in the female, IVF may be the best treatment choice.

When poor cervical mucus is the only cause of infertility treatment success rates are typically high.

Endometriosis

Endometriosis is a benign disease defined by the presence of ectopic ( outside the uterus ) endometrial tissue and stroma that can be associated with pelvic pain and infertility. Endometriosis exhibits a broad spectrum of clinical manifestations, is prone to progression and recurrence, and often presents difficult clinical management problems for women and their clinicians. Endometriosis is a major cause of infertility and may be present with no symptoms. Some studies indicate that endometriosis decreases pregnancy rates even though there may be little visible organ damage.

Most estimates of the prevalence of endometriosis range from 5% - 20% among women with pelvic pain and 20% - 40% among infertile women; a general prevalence of 3% - 10% in reproductive - aged women is likely.

The causes of endometriosis are not clearly understood, although the most accepted one is the theory of retrograde ( back flow ) menstruation and implantation. Endometriosis tends to cluster within families. It is six to seven times more prevalent among the first degree relatives of affected women than in the general population.

Endometriosis is strongly associated with infertility. In women with advanced stages of endometriosis, grossly distorted pelvic anatomy or tubal occlusion offers a logical explanation, but in women with milder disease, any mechanisms that may be responsible are less obvious. Indeed, whether minimal and mild degrees of disease can be regarded as a cause of infertility remains highly controversial. The infertility associated with endometriosis has been attributed to three primary mechanisms: distorted adnexal anatomy that inhibits or prevents ovum capture after ovulation, interference with oocyte development or early embryogenesis, and reduced endometrial receptivity.

Traditional medical therapies for endometriosis have reduced or eliminated cyclic menstruation. These include multiple medications with different side - effects: danazol, progestins, oral contraceptives, and GnRH agonists ( Lupron ). Overall, the effects of medical treatments on the volume of endometriosis are similar, but medical treatments are not effective for all but the smallest of ovarian endometriomas ( less than 1 cm ). Treatment with danazol or a GnRH agonist may decrease the size of endometriomas but does not eliminate them.
The objectives of surgical treatment of endometriosis is to restore normal anatomy, to excise or destroy all visible disease, and to prevent or delay recurrence of disease. Surgery for the treatment of endometriosis can be performed via laparotomy or laparoscopy. Laparoscopy offers the advantages of better visualization, less tissue trauma and desiccation, smaller incisions, and a shorter postoperative recovery. Deeply infiltrating endometriosis involving the rectovaginal septum requires extensive surgery.

In women with advanced symptomatic disease who have completed childbearing and those in whom medical and conservative surgical treatment fails, radical surgical treatment ( hysterectomy and bilateral removal of the tubes and ovaries ) merits serious consideration and discussion. The Endometriosis Association is an international organization that provides education and support for women with endometriosis.

Male Factor

Male infertility is present in 30% - 45% of infertile couples. This high frequency seems to be increasing in parallel with a possible overall decline of sperm numbers and function worldwide.

Therefore, the Jones Institute since its inception focuses on the development of new diagnostic methods in andrology and on the design of more efficient therapeutic modalities to help these couples achieve their reproductive goals.

Today, moderate and severe cases of male infertility are efficiently treated by the use of assisted reproductive technology ( ART ). Among these modalities, in vitro fertilization ( IVF ) and embryo transfer, augmented by intracytoplasmic sperm injection ( ICSI ), constitute formidable and successful means to achieve viable pregnancies in these groups of patients. ICSI has become a revolutionary alternative that offers a high chance of conception to men presenting with previously intractable or irreversible infertility.

It is mandatory for the male partner of all infertile couples to undergo a thorough physical examination followed by repeated semen analyses. The semen analysis should always include a state - of - the - art determination of the basic semen parameters ( i.e., sperm concentration, motility, morphology, and viability ) as well as an immunological ( presence of antisperm antibodies ) and a microbiological ( semen culture ) investigation. If needed, more advanced sperm function tests should be performed; for example, valuable information about sperm fertilizing capacity can be obtained through the assessment of sperm - zona pellucida binding ( using the hemizona assay ), acrosome reaction tests, and other bioassays. The Jones Institute is one of few programs that has a PhD andrologist devoted to semen analyses.

Hormonal evaluation and urologic consultation may be indicated in many cases. We have developed a close relationship with our urology colleagues in order to better understand and treat male infertility. Because of the ICSI "revolution," many cases can be approached through a combined effort of ART and urologic interventions. A testicular biopsy may be indicated in some cases to determine the potential use of testicular sperm for ICSI.

Our andrology staff is comprised of highly experienced technicians and co - directed by Sergio Oehninger, MD, PhD, and Mahmood Morshedi, PhD, HCLD, internationally known experts in andrology. We employ the Kruger Strict Criteria approved by the World Health Organization when evaluating semen. The following characteristics are assessed:
Semen volume - the amount of fluid that makes up the semen
Sperm count - the number of sperm present in a standard volume. A normal sample contains more than 20 million sperm per milliliter.
Motility - the percent of sperm moving when the semen is examined under the microscope. Normal is defined as >50% motile.
Progression - the forward movement of sperm cells
Viability - the percent of live sperm
Sperm morphology or shape
Additional semen contents, such as white blood cells, are an indication of infection. Less than five white blood cells per high power field is considered normal.

Spermatozoa ( sperm ) are relatively fragile cells and are easily damaged by a number of environmental and life style habits. Increased body temperature resulting from illness, prolonged periods of sitting in hot tubs, or tight clothing can affect sperm production and function. Strenuous repetitive exercise, such as long distance bicycling or marathon running, can also alter sperm production, as can significant weight loss or gain. Drugs, including alcohol and nicotine, can decrease male fertility and should be minimized or avoided while attempting to achieve pregnancy.

Many genetic diseases can impair male fertility, including Klinefelter's syndrome and cystic fibrosis. Exposure to environmental toxins, such as heavy metals and other chemicals, can also reduce male fertility.

Infections with microorganisms, such as chlamydia, mycoplasma, or niesseria gonorrhea, also can decrease fertility and are effectively treated with antibiotics. Rarely, a male will produce antibodies to his own sperm. When this occurs, his immune system mistakes his sperm for an invading pathogen and seeks to destroy them.

Hormonal imbalances, such as hypogonadotropic hypogonadism, can lead to male infertility. In this rare condition, gonadotropin releasing hormone ( GnRH ) , which is released from the hypothalamus, is deficient. GnRH controls the process leading to the production of testosterone and other reproductive hormones. Diseases of the pituitary gland also can lead to deficiencies of FSH and LH, which are hormones necessary for sperm production.

A varicocele, an enlargement of the veins to the testes ( spermatic cord ), may be present and usually occurs in the left testicle. The varicocele impairs the blood flow needed to cool the testicles, thus raising the temperature of the involved testicle. A varicocele may be accompanied by pain and often can be treated surgically by a urologist.

Retrograde ejaculation occurs when sperm are propelled "backwards" into the bladder rather than ejaculated through the penis. This condition can be caused by certain medications, previous surgery, spinal cord disease, diabetes, and other factors. Sometimes, it can be treated by removing the causative medication or by surgery.

Sperm production requires 90 days; an analysis done today reflects the state of "sperm development" three months prior. Unfortunately, in most cases there is no scientifically proven medication that will significantly increase sperm quantity or quality unless there is a specific organ disease that can be treated. Medications, such as Clomid and FSH, have been tried, but they must be administered for at least three months and are very expensive. Even so, improvement in sperm count is marginal.

Intrauterine insemination ( IUI ) with specially prepared sperm is often effective in treating mild male infertility. In this procedure, the sperm are obtained by masturbation, then washed, concentrated, and placed in the female's uterus via a small catheter.

In moderate to severe male factor infertility, donor sperm or IVF using the partner's sperm are the treatments of choice. Recent advances in assisted reproductive technologies, such as intracytoplasmic sperm injection ( ICSI ), enable men with moderate to severe male factor infertility to father a child. In ICSI, a single sperm is injected into the egg. The sperm can be obtained from the ejaculate or areas of the male reproductive tract, such as the testes. It is possible for a man with no sperm in his ejaculate to father a child.

The causes and treatments of male infertility are complex as is the evaluation; therefore, it is always best to seek care from a reproductive endocrinologist, a urologist specializing in infertility, and an andrologist.

Ovulation Disorders

Ovarian Failure

Delaying child bearing is more common today as more women focus on establishing their careers and decide to marry later. Although the life expectancy has increased, the reproductive window has not, with the average age of menopause remaining around 50 years. The decrease in fertility begins about age 35, and accelerates after age 37. Fertility is almost 0 by the age of 45. Along with the decrease in fertility, there is an increase in the risk of miscarriage, with a rate of 35% in women over 40 years of age. Women with premature menopause can experience this age related decline in fertility much younger.

The decrease in fertility with age is due mainly to ovarian aging and a decrease in ovarian reserve. Women are born with all the eggs that they will have throughout life. Every month, besides ovulation, several hundred eggs die in a process called atresia. Most women lose their best quality eggs earlier in their reproductive lives and the eggs that remain in the ovaries of women in their forties are mostly abnormal. These eggs offer fewer chances of fertilizing, implanting, and maintaining a normal pregnancy. Age is also associated with higher risks of chromosomal abnormalities, such as Down syndrome, which increases from 1 / 500 at 20 years of age to 1 / 20 at 45 years.

In addition to ovarian aging, uterine abnormalities, such as fibroids, polyps, adenomyosis, and other problems, such as endometriosis and scar tissue ( adhesions ), become more common as women age. Sperm count also is adversely affected by male age.

Treatment options in older women usually involve superovulation ( administration of ovulation inducing drugs ) to increase the number of eggs released per month. However, older women often respond poorly to the stimulation, thus IVF success rates are much lower than in younger women. The live birth rates per IVF attempt are approximately 15% for females at age 40 compared to less than 5% for females over 42.

Other strategies in older women undergoing IVF include assisted hatching of the embryos, or preimplantation genetic diagnosis, which allows the transfer of genetically normal embryos. Unequivocally, the highest success rates are seen with egg donation with pregnancy rates over 50% per IVF attempt.

Embryo donation, surrogacy, and adoption offer other options for fertility.

Decrease ovarian reserve and ovarian failure.

Although the average age of menopause is 51 years, some women experience ovarian failure and stop ovulating prior to age 40. Often, this is associated with an autoimmune disease, such as thyroid dysfunction or surgery on the ovary. Therefore, the Jones Institute performs hormonal testing to assess ovarian reserve in all women regardless of age, as well as ultrasound for ovarian volume and antral follicle count.

The reduction in number of follicles and eggs leads to a decrease in levels of estrogen and progesterone, resulting in elevated levels of FSH and LH. Most commonly, we measure the cycle serum levels of FSH, LH, estradiol, and sometimes inhibin B on day three. In cases of premature ovarian failure, karyotype ( chromosomal analysis ) and thyroid antibody testing is performed. Although 5 - 10% of patients with premature ovarian failure become pregnant, there is no proven method to increase the chance of conception in women with high FSH levels.

Low ovarian reserve is a good predictor of poor stimulation in ART and in combination with age predicts a low chance of pregnancy. Egg donation is recommended to these women.

PCOS

Tubal Disease

Tubal ligation ( severing the fallopian tubes ) is the most common form of permanent female sterilization and can usually be reversed surgically. Tubal reanastamosis ( reconnection of the tubes ) is a procedure performed through a mini laparotomy by a reproductive surgeon. The surgeon removes the blocked portion of the fallopian tubes and then microscopically sutures the tubes back together.

We offer tubal reanastamosis ( reconnecting the fallopian tubes ), which in otherwise fertile patients is the most successful type of tubal surgery. Success rates are usually between 50 and 80%, but vary according to where the tubes were cut, if scar tissue has formed, and other confounding factors. We offer both IVF and tubal reanastamosis. The best method depends on the patient's age, semen parameters, and method of sterilization.

Per cycle pregnancy rates are higher with IVF, thereby making IVF the treatment of first choice in older women. After tubal reversal, there is no limit to the number of times pregnancy may be attempted through intercourse. The number of repeat IVF cycles is often limited by cost. However, egg quality declines as females age, and numerous " natural " cycles after tubal reanastamosis may not be an option.

Before tubal reversal, a fertility evaluation is performed to ensure that ovulation occurs regularly and that there are no secondary causes of infertility. If other disorders are identified, they usually can be treated effectively.

Tubal reversal microsurgery should be performed by a reproductive surgeon with advanced training in microsurgery. The surgeons at the Jones Institute have undergone extensive advanced training and have vast clinical experience in laparoscopy and microsurgery.

Tubal Factor: Tubal Occlusion and Pelvic Adhesions

Tubal and peritoneal pathology is among the most common causes of infertility and the primary diagnosis in approximately 30% - 35% of infertile couples. A history of pelvic inflammatory disease ( PID ), septic abortion, ruptured appendix, tubal surgery, or ectopic pregnancy suggests the possibility of tubal damage.

Other causes of tubal factor infertility include inflammation related to endometriosis, inflammatory bowel disease, or surgical trauma. HSG and laparoscopy are the two classic methods for evaluation of tubal patency in infertile women and are complementary rather than mutually exclusive; each provides useful information that the other does not and each has advantages and disadvantages. HSG images the uterine cavity and reveals the internal architecture of the tubal lumen, neither of which can be evaluated by laparoscopy. Laparoscopy provides detailed information about the pelvic anatomy that HSG cannot, including adhesions, endometriosis, and ovarian pathology.

Distal tubal occlusive disease exhibits a wide spectrum of severity. HSG will generally reveal complete distal tubal obstructions but cannot reliably detect or define lesser degrees of disease when the tubes are patent. Laparoscopy is the definitive method for diagnosis of distal tubal occlusive disease and also provides the means for treatment. As might be expected, surgical outcomes are inversely related to the severity of disease. For the milder forms of distal tubal disease, postoperative term pregnancy rates can exceed 50%. Results achieved with surgery for more severe disease have varied widely but success rates are lower ( 10% - 35% ) and risk for ectopic pregnancy is higher ( 5% - 20% ). Postoperative tubal patency rates far exceed pregnancy rates; patency is more easily restored than function. The majority of pregnancies occur within the first two postoperative years.

Treatments

Ovulation Induction
IUI
IVF
ICSI
Donor Egg
Surgery

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