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Infertility
- 1. Infertility Version 1
- 24. Fertility Evaluation: General and Gynecological Examination Visual evaluation and pelvic exam for women to rule out: Visual evaluation and penile exam for men to rule out: Endocrinopathy Congenital anomalies Uterine hypoplasia Cervical lesions Dyspareunia Hypogonadism Tumors Epididymal cysts Cryptorchidism Hydrocele Varicocele
- 30. Treatment Possibilities: Female Infertility Ovulation disorders Ovulation-inducing drugs Hyperprolactinemia Prolactin-suppressing drugs Uterine and tubal abnormalities Surgical procedures Cervical mucus problems Intrauterine insemination Endometriosis Suppressing hormones or surgical procedure
- 32. Treatment of Female Infertility: Ovulation Induction Agents induces release of gonadotropins Gonadotropins Clomiphene citrate Gonadotropin releasing hormone analogs similar in structure to natural GnRH, provoke a massive release of GnRH into the circulation human menopausal gonadotropin (HMG), which contains equal quantities of FSH and LH Bromocriptine suppresses production of prolactin
Editor's Notes
- Slide 1. Infertility
- Slide 2. Infertility: Introduction Infertility is a significant social and medical problem affecting couples worldwide. The average incidence of infertility is about 15%. The incidence varies in different populations, in some areas approaching 40%. Some causes can be easily detected and treated, whereas others cannot. Approximately 10% of cases are unexplained, where no definitive cause can be identified.
- Slide 3. Definition of Infertility Infertility is defined as the inability to conceive after 12 months of having sexual intercourse with average frequency, without the use of any form of birth control. Intercourse 2 or 3 times per week may be considered average, although the frequency varies.
- Slide 4. Types of Infertility There are two types of infertility: primary and secondary. If a couple has never produced a pregnancy, it is defined as primary infertility. However, if the woman has previously been pregnant, regardless of the outcome (which may have been a premature or full-term delivery, spontaneous abortion, induced abortion or ectopic pregnancy), and is now unable to conceive, it is considered secondary infertility.
- Slide 5. Conception and Fertility The chance of conceiving in any given menstrual cycle is less than 20% in a woman of reproductive age. For conception to take place, several events should happen correctly and at exactly the right time. Three main events necessary for pregnancy to occur are: Ovulation: the process by which the mature egg is released from one of the woman’s ovaries. Fertilization: the process that takes place in the fallopian tube, when sperm unites with the egg. Implantation: the process when the fertilized egg attaches to the uterine wall. Any condition that interferes with these events may result in infertility.
- Slide 6. Factors Affecting Fertility: Frequency of Intercourse Various factors may adversely affect fertility. One of the common causes of infertility is infrequent intercourse. Coital frequency is positively correlated with pregnancy rates. A frequency of intercourse less than once per week results in a probability of conception of about 17% within 6 months. However, intercourse 3 times a week results in a probability of conception around 50% within 6 months. Although the sperm count may be slightly decreased by an intercourse frequency of once per day or once every other day, the motility and number of sperm in the healthy male would be sufficient to achieve pregnancy.
- Slide 7. Factors Affecting Fertility: Timing of Intercourse Intercourse prior to ovulation is key to maximizing the chance of pregnancy. Sperm can survive as long as 5 days in the female genital tract. The ovum has a much shorter life expectancy – less than 1 day if it is not fertilized. In fact, the “window of opportunity” for fertilization is thought to last only a few hours, thus requiring sperm availability in the female genital tract at or shortly before ovulation.
- Slide 8. Factors Affecting Fertility: STIs and Other Infections Gonorrhea and chlamidia in women can cause cervicitis and pelvic inflammatory disease (PID); and in men, urethritis, epididymitis, and, possibly, accessory gland infection. PID is a major cause of tubal infertility and can lead to ectopic pregnancy, which may further damage the reproductive system. Mumps, leading to orchitis (testicular inflammation), may cause secondary testicular atrophy in the small number of men infected after puberty. Other infectious diseases that may affect fertility include tuberculosis, toxoplasmosis, malaria, schistosomiasis and leprosy.
- Slide 9. Factors Affecting Fertility (Continued) Among other factors affecting the probability of conception are: Age of women. The effects of age on fertility are moderate and do not begin to take an effect until the late 30s. Older women take longer to conceive. Women attempting pregnancy at age 40 or older have a 50% decreased fertility rate and a two-fold to three-fold increased risk of spontaneous abortion compared with younger women. Age of men. A man’s age significantly affects coital frequency and sexual function. However, until approximately age 64, a man’s age does not affect sperm or the ability to fertilize eggs. Nutrition. Women who have a body weight 10% to 15% below normal may have reduced fertility. The percentage of body fat should be greater than 22% to permit regular ovulatory cycles. Obesity may also lead to less frequent ovulation or to less frequent intercourse, thereby contributing to fertility problems.
- Slide 10. Factors Affecting Fertility (Continued) Various toxic agents, smoking and alcohol may contribute to fertility problems. Exposure to toxic agents can occur from occupational hazards or contaminated air, water, food supply or other exposures. Lead, toxic fumes and exposure to pesticides are suspected contributors to infertility. In women, lead poisoning reduces conceptions and increases the risk of fetal wastage. In men, exposure to lead can reduce both sex drive and sperm count. Pesticide exposure can also reduce sperm count. In men, cigarette smoking and alcohol use may cause poor sperm quality, and marijuana use can also be implicated in lower sperm motility and count. In women, both smoking and alcohol use are associated with lower rates of conception and increased rates of spontaneous abortion.
- Slide 11. Infertility: Female and Male Factors It is very important to note that infertility can occur as a result of one or more male or female factors. Female and male factors are equally responsible for infertility, about 30% to 40% each, and in 20% of the cases, there is a combination of both. Therefore, it is particularly important to evaluate both partners when investigating infertility.
- Slide 12. Requirements for Female Fertility One of the requirements for female fertility is a functioning reproductive anatomy and physiology. It involves: A vagina capable of receiving sperm. Normal cervical mucus to allow passage of the sperm to the upper genital tract. Ovulatory cycles. Fallopian tubes that are patent and will function to permit the sperm and ovum to meet and allow migration of the conceptus to the uterus. A uterus capable of developing and sustaining the conceptus to maturity. Adequate hormonal status to maintain pregnancy.
- Slide 13. Requirements for Female Fertility (Continued) Other requirements for female fertility include: Adequate sexual drive and sexual function to permit coitus. Normal immunologic responses to accommodate sperm and conceptus. Adequate nutritional and health status to maintain nutrition and oxygenation of placenta and fetus.
- Slide 14. Requirements for Male Fertility. There are several requirements for male fertility. The man must be producing healthy sperm in quantities large enough to fertilize an egg cell. Thus one of the requirements is normal spermatogenesis – normal sperm count, motility and biologic structure and function. Another requirement for male fertility is a normal ductal system. Ductal blockage, as a result of an infection or congenital abnormality, may occur in the ducts that carry sperm from the testicles to the penis.
- Slide 15. Requirements for Male Fertility (Continued) The ability to transmit the spermatozoa to the female vagina is also important. This is achieved through: Adequate sexual drive. Ability to maintain an erection. Ability to achieve a normal ejaculation. Placement of ejaculate in the vaginal vault.
- Slide 16. Causes of Female Infertility The following causes may lead to infertility in women: Pelvic inflammatory disease, which can lead to blocked or damaged fallopian tubes. Damaged tubes may interfere with fertilization of the egg and its transport into the uterine cavity. Ovarian dysfunction, when a woman’s ovaries are not producing eggs, or egg production has diminished due to hormonal imbalance, age or other factors.
- Slide 17. Causes of Female Infertility (Continued) Other causes of female infertility include: Local factors in the uterus and cervix, including uterine septum, uterine fibroids and endometriosis. These factors may interfere with embryo implantation and a woman’s ability to carry pregnancy to term. Other factors, such as luteal phase defect or production of anti-sperm antibodies. A luteal phase defect results in low production of the hormone progesterone, which is necessary for maintaining a pregnancy. Low progesterone levels may lead to early miscarriage. The production of anti-sperm antibodies by the woman’s immune system can interfere with fertilization.
- Slide 18. Causes of Male Infertility Male infertility may be a result of some conditions that affect the quality of sperm, lead to low sperm production (oligospermia), or lead to the absence of sperm production (azoospermia). One of such conditions is a varicocele – one of the major causes of male infertility – that occurs when a vein that carries blood out of the scrotum dilates. It causes a blood stasis that raises the temperature of the scrotum. The elevated temperature hinders the maturation process of sperm, which develop best in an environment that is slightly cooler than body temperature. Other conditions that affect the quality and quantity of sperm include: Primary testicular failure. Accessory gland infection. Idiopathic low sperm motility.
- Slide 19. Causes of Infertility Affecting Both Partners Some causes of infertility, such as psychological causes, may be relevant to both partners. It is important to establish whether or not the couple really wants to have a child. Some couples experience pressure from society, parents and family, who expect that they wish to have children. The couples are not always consciously aware that they really are not interested in having children, but their sexual behavior reflects this attitude, e.g., in having sexual intercourse only after ovulation. Other causes of infertility affecting both partners include immunological incompatibility between sperm and the cervical mucus, which may in some instances cause sperm agglutination. In some couples who have been unable to reproduce, tests fail to find the cause of infertility. This may reflect an unknown immunological incompatibility or other unknown problem with fertilization or implantation.
- Slide 20. Basic Work-up for Infertility It is very important to remember that infertility can occur as a result of one or more male or female factors. Thus it is essential to evaluate both the man and the woman. A detailed history and physical examination is necessary for both partners. The basic work-up, or fertility evaluation, includes: Semen analysis of the male partner. Evidence that the woman ovulates. Checking the woman’s fallopian tubes to make sure they are not blocked. A postcoital test to determine if sperm are able to move through the cervical mucus is still performed by some clinicians. However, its value has been questioned because some studies have found no correlation between the presence or absence of viable sperm in the mucus and subsequent fertility.
- Slide 21. Fertility Evaluation Procedure Before the medical data are collected, the couple should be informed about the different causes of infertility, the tests and procedures required to make a diagnosis and the various therapeutic possibilities. After interviewing the couple together, the man and woman should be interviewed separately to obtain confidential information.
- Slide 22. Fertility Evaluation: General and Sexual History A detailed history includes: General history This includes occupation and background, use of tobacco, alcohol and drugs, earlier diseases, history of abdominal surgery and earlier infections. Sexual history – One of the purposes of obtaining a sexual history is to determine whether the partners have any sexual disturbance or dysfunction. Erectile dysfunction, vaginismus (painful involuntary spasm of vagina preventing intercourse) and dyspareunia (pain during sexual intercourse) can explain involuntary childlessness in some couples. A history of sexually transmitted infections could be another cause of infertility in either partner.
- Slide 23. Fertility Evaluation: Obstetric and Gynecological History The obstetric and gynecological history should include: Reproductive history (children, mode of delivery, prematurity, stillbirth, extrauterine pregnancy, spontaneous and induced abortion, fertility and infertility in earlier relationships). Gynecological history, including operations and medical treatment. Age at menarche. Menstrual periods: duration and intervals. Previous contraceptive use. Previous testing and treatment for infertility.
- Slide 24. Fertility Evaluation: General and Gynecological Examination For women, a visual evaluation of hair distribution and of body and breast development can indicate endocrinopathy or various development deficiencies. A complete pelvic exam should reveal any uterine hypoplasia, fibroids, adnexal tumors or cervical lesions and should indicate whether dyspareunia may be a problem. For men, a visual inspection of sexual characteristics can identify such endocrinopathies as hypogonadism (a condition resulting in atrophy or deficient development of secondary sexual characteristics) or Klinefelter’s syndrome (a genetic anomaly often associated with infertility). A penile exam should detect atrophy, tumors, epididymal cysts, cryptorchidism (undescended testicles), vas thickening or absence of the vas deferens, hydrocele (fluid accumulation in the testis or along the spermatic cord) or varicocele.
- Slide 25. Fertility Evaluation of the Female Partner: Evidence of Ovulation There are a variety of tests to check if and when the woman is ovulating. This can be done by a urine test, basal body temperature chart, progesterone test and/or endometrial biopsy. Urine test. Measures the LH in urine to detect if and when ovulation has occurred. Basal body temperature chart. After a woman ovulates, her body temperature rises by as much as 0.5° C. The woman is instructed to measures her body temperature every morning as soon as she wakes up, before she gets out of bed or before she eats or drinks anything. She records this temperature on a sheet of graph paper. The elevation in the temperature is indicative of ovulation. However, this method is not particularly accurate.
- Slide 26. Evaluation of the Female Partner: Evidence of Ovulation (Continued) Progesterone test. This test is based on the fact that the ovaries produce progesterone in the second half of the menstrual cycle after a woman has ovulated. A blood test done on days 21 or 22 of a normal 28-day menstrual cycle can be used to test whether ovulation has occurred by measuring the progesterone level. It also tests for a luteal phase defect (inadequate level of progesterone). Endometrial biopsy. The findings of the biopsy help determine whether the endometrium is adequately developed to support implantation and growth of a fertilized egg. The procedure is done during the premenstrual phase, approximately 12 days after presumed ovulation to see if the endometrium undergoes expected changes. A 2.0 mm flexible plastic tube is inserted into the uterine cavity through the cervix and a small piece of endometrial tissue is sampled using suction. This procedure is performed in the doctor’s office without anesthesia.
- Slide 27. Evaluation of the Female Partner: Other Tests Other tests to evaluate a woman’s fertility include: Hysterosalpinogram (HSG). This test is performed early in the menstrual cycle after bleeding has stopped but prior to ovulation. Radiopaque dye is instilled into the uterine cavity through the cervix and x-rays are taken. The dye outlines the cavity of the uterus and spills out of the fallopian tubes. This indicates whether the fallopian tubes are open or blocked. If they are blocked, it indicates the site of the block. It also shows if there are any abnormalities in the uterine cavity, such as polyps or submucous fibroids; or abnormalities of the tubes, such as evidence of salpingitis. Laparoscopy. This allows the physician to evaluate the woman for any pelvic disease, particularly endometriosis, which may interfere with conception. The patency of the fallopian tubes can also be checked. Hysteroscopy. The uterine cavity is distended with a gas or liquid, and the hysteroscope is introduced into the uterine cavity which can then be carefully inspected. Polyps and submucous fibroids can be removed during this procedure.
- Slide 28. Fertility Evaluation of the Male Partner: Semen Analysis Semen analysis is an essential part of the evaluation. The man is advised not to ejaculate for 2 to 3 days before giving the semen sample for evaluation. Because the sperm have a short life span outside the human body, the semen specimen must be evaluated within a short time frame. The semen is studied for a number of factors. An adequate semen analysis includes the following: Volume (1.5 cc to 5.0 cc). Number of sperm present (> 20 million/ml). Their ability to move (> 60%) and forward progression (more than 2 on a 1-to-4 scale). Morphology (> 60% normal forms). Absence of any infection.
- Slide 29. Fertility Evaluation of the Male Partner: Other Tests Other tests for men include: Urine analysis to rule out an infection. Endocrine tests to check concentrations of the hormones testosterone, FSH and LH. Anti-sperm antibodies. The presence of anti-sperm antibodies have been found in infertile men, and suppression of these antibodies with corticosteroid treatment has improved the semen quality and increased the rate of conception. Sperm penetration assay. This test measures the ability of the sperm to penetrate a specially prepared egg from an animal, usually a hamster. Postcoital test. Used by some clinicians to evaluate the motility of the sperm and its ability to travel through the cervical mucus. The validity of this test is low.
- Slide 30. Treatment Possibilities: Female Infertility Depending on the cause of infertility, there are different possibilities for treatment. Ovulation disorders can be treated with ovulation-inducing drugs. In women whose ovulation is suppressed by hyperprolactinemia (high blood levels of the pituitary hormone prolactin), ovulation may be induced with prolactin-suppressing drugs. Some uterine and tubal abnormalities, such as adhesions, uterine septum, or fibromyoma, may be corrected by surgical procedures. Cervical mucus problems impairing conception may be treated with intrauterine insemination (IUI) or uterine instillation of specially prepared sperm. Endometriosis can be treated with hormones that suppress the displaced endometrial tissue or the tissue can be removed by a surgical procedure.
- Slide 31. Treatment of Female Infertility: Induction of Ovulation Ovulation induction involves the use of medication to stimulate development of one or more mature follicles in the ovaries of women who have anovulation and thus are infertile. Ovulation induction is somewhat different from controlled ovarian hyperstimulation, which involves the use of some of the same medications to stimulate the development of multiple mature follicles and eggs in order to increase pregnancy rates with various infertility treatments. Success rates for induction of ovulation vary considerably and depend on the age of the woman, the type of medication used, the presence of other infertility factors present in the couple and other reasons.
- Slide 32. Treatment of Female Infertility: Ovulation Induction Agents The main agents used for the induction of ovulation include: Clomiphene citrate is an orally active, nonsteroidal agent structurally similar to estrogen. This similarity is sufficient to achieve binding by estrogen receptors, including the receptors of the hypothalamus. The hypothalamus acts on the false information that the estrogen level in circulation is low, increasing production of FSH and LH, thus stimulating follicular growth. Gonadotropin releasing hormone analogs (GnRH-a) are synthetic peptides whose structure is similar to the natural GnRH. They compete with endogenous GnRH molecules for the pituitary receptors and provoke a massive release of gonadotropins into circulation. The increase of gonadotropins can provoke ovulation. Gonadotropins are available in the form of human menopausal gonadotropin (HMG) derived from the urine of postmenopausal women. HMG contains equal quantities of FSH and LH and are administered intramuscularly. Bromocriptine is used in cases when anovulation is caused by an elevated level of the hormone prolactin. This is an uncommon type of anovulation disorder.
- Slide 33. Treatment of Female Infertility: Intrauterine Insemination Intrauterine insemination (IUI) is a fertility procedure in which sperm are washed (separated from the semen), concentrated, and injected directly into a woman’s uterus. In natural intercourse, only a fraction of the sperm make it into the woman’s genital tract. IUI increases the number of the sperm in the fallopian tubes, where fertilization takes place. IUI with the partner’s sperm can be used as a potentially effective treatment for infertility in women under age of 45 except for cases with tubal blockage, very poor egg quality, ovarian failure and severe male factor infertility (very low sperm count or very poor sperm shape or mobility). Studies show that the IUI is most successful when it is coupled with fertility drugs to enhance ovulation, with success rates between 5% and 20% per cycle.
- Slide 34. Treatment of Female Infertility: Assisted Reproductive Technology (ART) Assisted Reproductive Technology (ART) is a term used to collectively describe a number of noncoital methods of conception that treat causes of infertility not responsive to conventional methods. ART includes all fertility treatments in which both eggs and sperm are manipulated. In general, ART involves surgically removing eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the woman’s body. It does not include procedures in which only sperm are manipulated, such as intrauterine insemination, or procedures in which a woman takes drugs only to stimulate egg production, without the intention of having eggs retrieved. The types of ART include: In Vitro Fertilization (IVF) Gamete Intrafallopian Transfer (GIFT) Zygote Intrafallopian Transfer (ZIFT) Another ART procedure – Intracytoplasmic Sperm Injection (ICSI) – is used mainly in cases of male infertility to treat couples who cannot achieve fertilization due to the male partner’s extremely low number of normal, viable sperm.
- Slide 35. ART: In Vitro Fertilization In Vitro Fertilization (IVF) is a procedure that involves retrieving eggs and sperm from the female and male partners and placing them together in a laboratory dish to enhance fertilization. Fertilized eggs are then transferred several days later into the woman’s uterus, where implantation and embryo development will hopefully occur as in a normal pregnancy. In order to maximize the patient’s chances for successful fertilization, physicians typically use ovarian stimulation medications rather than using the single egg normally developed each cycle. Success rates with IVF procedure are approximately 20% per egg retrieval (approximately 20 couples out of every 100 who try one retrieval with IVF are likely to achieve pregnancy and delivery).
- Slide 36. ART: Gamete Intrafallopian Transfer (GIFT) GIFT is a procedure that involves ovarian stimulation, egg retrieval, and placing a mixture of sperm and eggs directly into the woman’s fallopian tube to foster fertilization inside the female body. One of the requirements for this procedure is that a woman should have at least 1 undamaged fallopian tube. Unlike IVF, in which actual fertilization is observed and confirmed in the laboratory, GIFT does not allow visual confirmation of fertilization. If fertilization occurs, the developing embryos remain in the fallopian tube and then move to the uterus for the natural implantation process to be completed. In terms of deliveries per egg retrieval, GIFT has a higher success rate than IVF regardless of the woman’s age – approximately 28%.
- Slide 37. Zygote Intrafallopian Transfer (ZIFT) Zygote Intrafallopian Transfer (ZIFT) is another variation of IVF. ZIFT is often called “tubal embryo transfer.” As with IVF, the actual fertilization of the eggs is observed and confirmed in the laboratory. Afterwards, fertilized eggs are placed directly into a fallopian tube (as with GIFT) and not into the uterine cavity. The success rate is about 29% per egg retrieval.
- Slide 38. Treatment Possibilities: Male Infertility Surgical treatment may be successful in some cases, such as varicocele. In cases of poor sperm quality, intrauterine insemination can be performed. It can be done with a patient’s sperm, if possible. In cases when the quality of sperm is very poor, or sperm is completely absent in the ejaculate (azoospermia), donor’s sperm can be used (if culturally acceptable). ART procedures, such as GIFT, IVF, and ICSI, also can be used in cases of male infertility. Donor semen should be free from any STI-producing organisms, including HIV.
- Slide 39. ART: Intracytoplasmic Sperm Injection (ICSI) Another ART procedure Intracytoplasmic Sperm Injection (ICSI) involves the injection of a single sperm into the egg. The ICSI process takes place following a cycle during which fertility drugs are administered to the female partner to aid in the production of multiple eggs. Only active, undamaged sperm are chosen for injections. Once eggs and sperm are collected, the actual process of injecting a single sperm into the egg is carried out in a laboratory using a petri dish or a glass slide with a well in the center.
- Slide 40. ART: Intracytoplasmic Sperm Injection (ICSI) (Continued) Once an egg is injected, it is observed for approximately 14 hours to see if fertilization has occurred (average fertilization rate is about 65%), and for 24 hours to ensure that cell division has started. If each step has occurred as planned, implantation of the fertilized egg into the uterus can take place within 72 hours of the ICSI process. Success rates reported by various practices that offer ICSI range from 15% to 30% per egg retrieval.
- Slide 40. Infertility: Summary Infertility is a significant social and medical problem affecting couples worldwide. Female and male factors are equally responsible for infertility. Evaluation of both partners is essential. Treatment depends on the cause of infertility and varies from ovulation-inducing drugs to surgery to ART.