1. INFERTILITY

2. Infertility: Introduction
Significant social and medical problem affecting couples worldwide
Average incidence of infertility is about 15% globally
varies in different populations
Some causes can be detected and treated, whereas others cannot
unexplained infertility constitutes about 10% of all cases
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.

3. Definition of Infertility
Inability to conceive after 12 months of having sexual intercourse with average frequency (2 to 3 times per week), without the use of any form of birth control
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.

4. DEFINITION of Infertility
What is Infertility?
Infertility is defined two years of unprotected intercourse without pregnancy.
(WHO, one year)
What is sterility?
Absolute inability to conceive

5. Types of Infertility Primary infertility Secondary infertility
couple has never produced a pregnancy
Secondary infertility
woman has previously been pregnant, regardless of the outcome, and
now is unable to conceive
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.

6. Conception and Fertility
The chances of conceiving in any given menstrual cycle is less than 20%
Main events necessary for pregnancy to occur are:
ovulation
fertilization
implantation
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.
Any condition that interferes with these events may result in infertility

7. Factors Affecting Fertility: Timing of Intercourse
Intercourse just before ovulation maximizes the chance of pregnancy
Sperm survives as long as 5 days in the female genital tract
Ovum life expectancy is about 1 day if not fertilized
Sperm should be available in the female genital tract at or shortly before ovulation
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.

8. Requirements for Male Fertility
Normal spermatogenesis in order to fertilize egg:
sperm count
motility
biological structure and function
Normal ductal system to carry sperm from the testicles to the penis
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.

9. Requirements for Female Fertility
Adequate sexual drive and sexual function
Normal immunologic responses to accommodate sperm and conceptus
Adequate nutritional and health status to maintain nutrition and oxygenation of placenta and fetus
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.

10. Factors Affecting Fertility: STIs and Other Infections
Gonorrhea and chlamydia can cause:
in women: pelvic inflammatory disease (major cause of tubal infertility) and cervicitis
in men: urethritis, epididymitis, accessory gland infection
Mumps, leading to orchitis, may cause secondary testicular atrophy
Other infections that may affect fertility include tuberculosis, toxoplasmosis, malaria, schistosomiasis and leprosy
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.

11. Factors Affecting Fertility (Continued)
Age of the woman
after 40 the fertility rate decreases by 50% while the risk of miscarriage increases
Age of the man
increased age affects coital frequency and sexual function
Nutrition
for women, weight 10% to15% below normal or obesity may lead to less frequent ovulation and reduced fertility
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.

12. Factors Affecting Fertility (Continued)
Factors that can contribute to fertility problems include:
toxic agents, such as lead, toxic fumes and pesticides
smoking and alcohol
All these factors may cause:
in women: reduced conceptions and increased risk of fetal wastage
in men: reduced sex drive and sperm count
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.

13. Infertility: Female and Male Factors
Infertility may be a result of one or more male or female factors
Female and male factors are equally responsible for infertility (30% to 40% each)
in 20% of cases there is a combination of both factors
Evaluating both partners is essential
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.

14. Causes Causes Percentage Female factors 40-55 % Male factors 25-40 %
Both male and
female factors %
unexplained factors %

15. Female Factors Ovulatory dysfunction: 1. Hypothalamic dysfunction;
2. Pituitary Insufficiency;
3. Ovarian factor (peripheral defect);
4. Others: thyroid or adrenal dysfunction;
Pelvic factorsP:
1. Tubal factors: injury, blockage, adhesion;
2. Uterine factors;
3. Cervical factors;
4. Extra-genital tract factors;

16. Causes of Female Infertility (Continued)
Local factors in the uterus and cervix
may interfere with implantation and woman’s ability to carry pregnancy to term
Luteal phase defect
results in low production of progesterone
may lead to early miscarriage
Production of anti-sperm antibodies
can interfere with fertilization
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.

17. Female Factors Follopian tube Uterine ovary oocyte Cervix
Hypothalamus
Pituitary
Follopian tube
Uterine
ovary oocyte
Cervix
Extra-genital tract
sperm
Thyroid
Adrenal

18. Male Factors 1. Abnormal spermatogenesis congenital; chronic diseases;
infectious factors;
2. Obstructive;
3. Immunologic factors;
4. Endocrine disorders;
5. Sexual dysfunction;

19. Causes of Male Infertility
Conditions that affect quality or quantity of sperm may lead to infertility
These conditions include:
varicocele
primary testicular failure
accessory gland infection
idiopathic low sperm motility
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.

20. Both Male and Female Factors
1. No demonstrable cause;
2. Psychological factors;
3. Immunologic factors;
count for 10%;
autoimmune response;
auto-antibodies;

21. Initial Visit The initial visit is the most important;
The infertility is a problem of couple;
The male partner should be present;
History: both male and female;
The guide to diagnostic and treatment plans;

22. Basic Work-up for Infertility
Evaluating both partners is essential
Detailed history and physical examination for both
Semen analysis
Evidence of ovulation
Evidence of fallopian tubes patency
Postcoital test
still performed by some clinicians
not found valid by some studies
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.

23. Fertility Evaluation Procedure
Couple should be informed about:
different causes of infertility
tests and procedures required to make a diagnosis
various therapeutic possibilities
Couple’s interview is conducted together as well as separately to obtain confidential information
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.
Richard Lord

24. Fertility Evaluation: General and Sexual History
General history
occupation and background
use of tobacco, alcohol and drugs
history of abdominal surgery and earlier diseases/infections
Sexual history
sexual disturbances or dysfunction such as vaginismus, dyspareunia or erectile dysfunction
sexually transmitted infections
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.

25. Fertility Evaluation: Obstetric and Gynecological History
Reproductive history
Gynecological history
Age at menarche
Menstrual periods: duration and intervals
Previous contraceptive use
Previous testing and treatment for infertility
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.

26. Examinations Physical examination; Bimanual examination
Rectal-Vaginal-examination
Laboratory;
Assistant imaging;

27. 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
Hypogonadism
Congenital anomalies
Tumors
Uterine hypoplasia
Epididymal cysts
Cervical lesions
Cryptorchidism
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.
Dyspareunia
Hydrocele
Varicocele

28. Examinations Laboratory: semen analysis hormone measurement;
sperm penetration assay (SPA)
postcoital examinition of cervical mucus
immunologic examination;
Assistant imaging :
Unltrasound
Hysterosalpingogram
Hysteroscopy
Laparoscopy

29. Fertility Evaluation of Male Partner:
Urine analysis: to rule out infection
Endocrine tests: to measure concentrations of hormones testosterone, FSH and LH
Anti-sperm antibodies
Sperm penetration assay: to establish ability of sperm to penetrate egg
Postcoital test (low validity): to establish ability of sperm to penetrate cervical mucus
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.

30. Normal Values for Semen Analysis
Volume > 2.0 mL
Sperm concentration > 20 million/mL
Motility >50 %
morphology >30 % normal
Data from WHO, 1992

31. Fertility Evaluation of Female Partner Examination and Diagnoses
Initial evaluation
History
Physical exam
Irregular menses
No ovulation
HSG
Tubal blockage
Normal
evaluation
HSG or
Hysteroscopy
Abnormal of
uterine
Abnormal
Semen
analysis
anovulation
Tubal factor
unexplained
Uterine factor
Male factor
Further Investigate and Treatment

32. Methods to monitor ovulation
Luteinizing Hormone monitoring:
LH surge;
after hr occur ovulation;
Basal Body Temperature: simple, cheap,
biphasic pattern;
Mid-luteal serum progesterone: > 3ng/mL, peak;
Premenstrual molimina: 95% presence;
Mucus change: thick and cellular, no crystalline fern;
Ultrasound monitoring: follicle size mm,
fluid in the cul-de-sac.

33. Evidence of Ovulation Ovulation can be established based on:
Urine test
measures the LH in urine to detect if and when ovulation occurred
Basal body temperature chart
temperature is measured every morning, before woman gets out of bed
elevation in temperature indicates ovulation
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.

34. Progesterone test Endometrial biopsy
progesterone level in blood is measured on days 21 or 22 of 28-day cycle
Endometrial biopsy
done during premenstrual phase
detects if endometrium undergoes expected changes (consistent with ovulation and production of progesterone)
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.

35. Fertility Evaluation of Female Partner: Other Tests
Hysterosalpinogram (HSG)
to determine whether fallopian tubes are blocked
Laparoscopy
to evaluate for pelvic disease, such as endometriosis, and check patency of fallopian tubes
Hysteroscopy
to evaluate condition of uterine cavity (polyps, fibroids)
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.

36. Treatment-female factor
Causes Treatment
induction of ovulation；
tuboplasty,
microsurgery；
medication or surgery；
immune inhibition；
anovulation
Tubal factor
Anatomic factor
immunologic
azoospermia
Assisted Reproductive Technologies
(ART)
genetic disease
after surgery
unexplained

37. Treatment Possibilities: Female Infertility
Ovulation disorders
Ovulation-inducing drugs
Hyperprolactinemia
Prolactin-suppressing drugs
Uterine and tubal abnormalities
Surgical procedures
Cervical mucus problems
Intrauterine insemination
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.
Endometriosis
Suppressing hormones
or surgical procedure

38. Treatment of Female Infertility: Induction of Ovulation
Involves the use of medication to stimulate development of one or more mature follicles
Success rates vary considerably and depend on age of the woman, the type of medication used, whether there are other infertility factors present in the couple and other reasons
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.

39. Induction of ovulation
1. Clomiphen ：ER binding GnRH ,FSH/LH
dosage：50 mg, period day 5th， 5days；
2. Gonadotropin therapy ：
Indications:
Hypogonadotropic hypogonadism;
Pituitary dysfunction;
COH (controlled ovarian hyperstimulation) in IVF;
HMG: human menopausal gonadotropins;
FSH 75 IU/LH 75 IU, IM or SC;
Recombinant FSH: 75 IU, SC;
3. HCG: IU;

40. Assisted Reproductive Technologies (ART)
Intrauterine insemination ( IUI)
In vitro fertilization and embryo transfer
(IVF-ET) Intracytoplasmic sperm injection (ICSI);
Gamete intrafallopian transfer (GIFT)

41. Intrauterine insemination ( IUI)
Indications:
1. as treatment of male factor infertility;
2. psychological factors;
3. unexplained infertility;
4. genetic defects;
Types:
1. artificial insemination with husband’s sperm (AIH);
2. artificial insemination by donor (AID);
Method:
placement of about 0.3 ml of washed, processed
and concentrated sperm into the intrauterine cavity
by trans-cervical catheterizaion.

42. In vitro fertilization and embryo transfer (IVF-ET)
Indications:
1. tubal factor;
2. endometriosis;
3. unexplained infertility;
4. IUI failure;
5. Immunologic factors;
Method:
1. Superovulation: COH, GnRH-a/FSH(HMG)/HCG;
2. Aspiration of eggs;
3. Fertilization with capacitated sperm;
4. Culture of fertilized egg in the lab;
5. Replacement of fertilized egg into the uterus;

43. Gamete intrafallopian transfer (GIFT)
Indications:
1. unexplained infertility;
2. endometriosis;
3. IUI failure;
4. Premature ovarian failure (POF);
5. Immunologic factors;
Method:
1. Superovulation is induced as IVF-ET;
2. HCG injection is given;
3. Follicle are aspirated via laparoscopy;
4. Sperm mixed with egg;
5. Replacement of fertilized egg into fallopian tube;

44. ART Complications Multiple gestations Pre-eclampsia
Ovarian hyperstimulation syndrome (OHSS)
Premature birth
Low birth weight
Long term emotional, social and psychological impact

45. Infertility: Summary
Infertility is a significant social and medical problem affecting couples worldwide
Female and male factors are equally responsible
Evaluation of both partners is essential
Treatment depends on the cause of infertility and varies from ovulation-inducing drugs to surgery to ART
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.