INFERTILITY Infertility Introduction Significant social and medical problem

INFERTILITY

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

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

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

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

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

Factors Affecting Fertility: Timing of Intercourse just before ovulation maximizes the chance of pregnancy l l l 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

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

Requirements for Female Fertility l l l 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

Factors Affecting Fertility: STIs and Other Infections l Gonorrhea and chlamydia can cause: - l l 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

Factors Affecting Fertility (Continued) l Age of the woman - l Age of the man - l after 40 the fertility rate decreases by 50% while the risk of miscarriage increases increased age affects coital frequency and sexual function Nutrition - for women, weight 10% to 15% below normal or obesity may lead to less frequent ovulation and reduced fertility

Factors Affecting Fertility (Continued) l Factors that can contribute to fertility problems include: - l 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

Infertility: Female and Male Factors l l 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) - l in 20% of cases there is a combination of both factors Evaluating both partners is essential

Causes Female factors Male factors Both male and female factors unexplained factors Percentage 40 -55 % 25 -40 % 10 %

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

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

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

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

Causes of Male Infertility l l 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

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

Initial Visit n n n 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;

Basic Work-up for Infertility Evaluating both partners is essential l l 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

Fertility Evaluation Procedure Couple should be informed about: l 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 Richard Lord l

Fertility Evaluation: General and Sexual History l General history - l 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

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

Examinations n n n Physical examination; Bimanual examination Rectal-Vaginal-examination Laboratory; Assistant imaging;

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 Dyspareunia Hydrocele Varicocele

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

Fertility Evaluation of Male Partner: l l l 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

Normal Values for Semen Analysis Volume Sperm concentration Motility morphology Data from WHO, 1992 > 2. 0 m. L > 20 million/m. L >50 % >30 % normal

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

Methods to monitor ovulation n n n Luteinizing Hormone monitoring: LH surge; after 34 -36 hr occur ovulation; Basal Body Temperature: simple, cheap, biphasic pattern; Mid-luteal serum progesterone: > 3 ng/m. L, peak; Premenstrual molimina: 95% presence; Mucus change: thick and cellular, no crystalline fern; Ultrasound monitoring: follicle size 21 -23 mm, fluid in the cul-de-sac.

Evidence of Ovulation can be established based on: l Urine test - l 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

l Progesterone test - l 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)

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

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

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

Treatment of Female Infertility: Induction of Ovulation l l 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, whethere are other infertility factors present in the couple and other reasons

Induction of ovulation n 1. Clomiphen ：ER binding Gn. RH , FSH/LH dosage： 50 mg, period day 5 th， 5 days； 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: 5000 -10000 IU;

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

Intrauterine insemination ( IUI) n n n 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.

In vitro fertilization and embryo transfer (IVF-ET) n n Indications: 1. tubal factor; 2. endometriosis; 3. unexplained infertility; 4. IUI failure; 5. Immunologic factors; Method: 1. Superovulation: COH, Gn. RH-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;

Gamete intrafallopian transfer (GIFT) n n 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;

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

Infertility: Summary l l 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