INFERTILITY work up in males and females

Endocrine

1. INFERTILITY

2. Definition It is inability to conceive after one year of unprotected relationship 25% of couples will experience an episode of infertility It is of 2 types Primary infertility Secondary infertility

3. Types of Infertility Primary Infertility Refers to couples or patients who had no previous successful pregnancies Secondary Infertility Refers to couples who have previously conceived, but are currently unable to conceive Infertility problems arise as a result of hormonal dysfunction of hypothalmic -pituitary- gonadal axis

4. Male Infertility It often goes undetected because low sperm count or abnormal sperm motility combined with normal female reproductive function results in delayed conception Testosterone is essential for normal sperm development Hypogonadism (low testosterone concentrations) results in infertility Causes include both hypogonadotropic & hypergonadotropic hypogonadism Most common cause of hypothalmic hypogonadism is congenital idiopathic hypogonadotropic hypogonadism (IHH) or Kallmann syndrome

5. MALE INFERTILITY FACTORS ENDOCRINE DISORDERS Hypothalamic dysfunction( Kallmann syndrome) Pituitary failure( tumor,radiation,surgery ) Hyperprolactinemia ( drug,tumor ) Exogenous androgens Thyroid disorders Adrenal hyperplasia Testicular failure

6. MALE INFERTILITY FACTORS ANATOMICAL Congenital absence of vas deferens Obstructed vas deferens Congenital abnormalities of ejaculatory system Varicocele Retrograde ejaculation ABNORMAL SPERMATOGENESIS Unexplained azospermia Chromosomal abnormalities Mumps orchitis Cryptochidism Chemical or radiation exposure

7. MALE INFERTILITY FACTORS ABNORMAL MOTILITY Absent cilia( Kartagener syndrome) Antibody formation PSYCHOSOCIAL Unexplained impotence Decreased libido OTHER CAUSES Anxiolytics Antihypertensives Thyroid disorders Adrenal hyperplasia Testicular failure

8. EVALUATION OF MALE INFERTILITY Laboratory evaluation of male infertility includes Semen analysis Endocrine parameters Immunological parameters SEMEN ANALYSIS Semen analysis measures Ejaculate volume pH Sperm count Motility Forward progression

9. NORMAL SEMINAL FLUID VALUES PARAMETER VALUE Ejaculate volume >2ml Sperm density >20million/ml Total sperm count >40million/ejaculate Motility >50% with forward progression or >25% with rapid progression with 60min of ejaculation Morphology >30% normal pH 7.2-8.0 colour Grey-white-yellow Liquefaction Within 40 mins

10. NORMAL SEMINAL FLUID VALUES PARAMETER VALUE Fructose >1200µg/ml Acid phosphatase 100-300µg/ml Citric acid >3mg/ml Inositol >mg/ml Zinc >75µg/ml Magnesium >70µg/ml Prostaglandins(PGE1+PGE2) 30-200µg/ml Glycerylphosphorylcholine >650µg/ml Carnitine >250µg/ml Glucosidase >20mU per ejaculate

11. EVALUATION OF ENDOCRINE PARAMETERS Borderline or supressed testosterone concentrations are evaluated with an CG stimulation test An I/M injection of 5000 IU CG is adminintered following collection of basal,early morning serum specimen for subsequent measurements of testosterone concentrations Second specimen is obtained 72hrs later & testosterone concentration is measured Hypogonadal men show depressed rise in testosterone concentration in response to this challenge Doubling of testosterone conc over baseline is consistent with normal leydig cell function Failure to increase testosterone >150ng/ml indicates primary hypogonadism

12. HYPERGONADOTROPIC HYPOGONADISM FSH measurement is indicated in men with sperm counts of <5 to 10 million/Ml Elevated concentrations of FSH indicates sertoli cell dysfunction In azospermic men there is primary germinal cell failure,sertoli cell only syndrome or genetic conditions like Klinefelter syndrome Elevated FSH(>120mIU/ mL ) in setting of decreased testosterone(<200ng/ dL ) & oligospermia indicates primary testicular failure or andropause

13. HYPOGONADOTROPIC HYPOGONADISM Decreased conc of testosterone (<200ng/dl) & decreased conc of FSH(<10mIU/ mL ) are suggestive of hypogonadotropic hypogonadism Administration of GnRH may help to distinguish b/w gonadal insufficiency caused by pituitary versus hypothalmic failure Patients with long standing hypogonadism should be given exogenous testosterone for one wk before GnRH stimulation test I/V inj 100µg of GnRH with measurement of FSH & LH concentrations at 0,30,60,120 & 180mins after injection Rise in serum gonadotropins≥10mIU/ mL over baseline is normal Patients with hypothalmic disease will demonstrate a delayed but significant increase in ≥7mIU/Ml within 180 mins

14. EVALUATION OF IMMUNOLOGICAL PARAMETERS Immunobead technique is most widely used In this technique a polyacrylamide bead is coated with a rabbit antihuman antibody It binds to antibodies that are already present on human sperm or present after incubation of sperm with appropriate fluid(cervical mucus or serum) This tech allows determination of percentage of human sperm bound immunoglobulin isotype Practice of testing for antisperm antibodies is noe recommended Antisperm antibodies are associated with infertility Concentration at which these decrease fertility is unknown

15. FEMALE INFERTILITY Female infertility factors are OVARIAN OR HORMONAL FACTORS METABOLIC DISEASE Thyroid Liver Obesity Androgen excess Polycystic ovarian syndrome

16. FEMALE INFERTILITY FACTORS HYPERGONADOTROPIC HYPOGONADISM Menopause Luteal phase deficiency Gonadal dysgenesis Premature ovarian failure( autoimmune,cytotoxic chemotherapy,tumor ) Resistant ovary syndrome HYPOGONADOTROPIC HYPOGONADISM Hyperprolactinemia ( tumor,drugs ) Hypothalmic insufficiency( Kallmann syndrome) Pituitary insufficiency( tumor,necrosis,stress,exercise,anorexia )

17. FEMALE INFERTILITY FACTORS TUBAL FACTORS Occlusion or scarring Salpingitis isthmica nodosa Infectious salpingitis CERVICAL FACTORS Stenosis Inflammation or infection Abnormal mucus viscosity UTERINE FACTORS Leiomyomata Congenital malformations Adhesions Endometritis or abnormal endometrium

18. FEMALE INFERTILITY FACTORS PSYCHOSOCIAL FACTORS Decreased libido Anorgasmia IATROGENIC IMMUNOLOGICAL(ANTISPERM ANTIBODIES) OVULATORY FACTORS Ovulatory dysfunction manifests itself in presence or absence of normal menses Metabolic diseases affect ovulatory function PCOS is the most common cause of anovulation CAH should be considered 21-hydroxylase deficiency or 3ß-hydoxysteroid deficiency may be present in 26% cases

19. EVALUATION OF FEMALE INFERTILITY In evaluation of female infertility should include Detailed history Physical examination PAP smear Rule out tubal pregnancy,endometriosis or adhesions Assessment of ovulation & adequate luteal function Post-coital test helps to determine coital sufficiency

20. POSTCOITAL TEST Postcoital test is quick assessment of multiple factors Test is schedulaed around time of LH surge Sterile speculum examination is performed 9 to 24hrs after intercourse Sample of endocervical mucus is aspirated & placed onto a glass slide with two coverslips Mucus with adequate estrogen stimulation appears clear & thin & forms a thread 6cm or greater in length when cover slips are separated from the slide

21. POSTCOITAL TEST When it is examined under microscope mucus air is dried under second cover slip & forms fern like pattern when adequate estrogen is present Before mucus is dried >20 motile sperm per high-power field should be visualized Normal test result suggests Coital sufficiency Probable ovulation Non-hostile cevical mucus Normal male fertility test Predictive values vary from 50% chance of conception within one year with optimal test to 15 % chance of conception if test is abnormal

22. EVALUATION OF OVULATION Measurement of midluteal plasma progesterone indicates corpus luteum was formed Other methods include basal body temperature Evaluation of LH surge PROGESTERONE MEASUREMENT Increase in progesterone concentrations indicate corpus luteum has been formed But cannot confirm whether egg was released Immediately after ovulation serum progestrone conc rise Peak within 5 to 9 days during midluteal phase

23. PROGESTERONE MEASUREMENT If ovulation does not occur corpus luteum fails to form Midluteal progesterone concentrations of >10ng/ml indicates normal ovulation Concentrations less than <10ng/ml suggest Anovulation Inadequate luteal phase progesterone production Inappropriate timing of sample collection

24. BASAL BODY TEMPERATURE Simple Cost effective indicator of ovulation Rapid rise in body temperature by 0.5ºF Persists through luteal phase Rise in temperature is due to increased concentration of progesterone

25. MEASUREMENT OF LH SURGE LH appears in urine just after serum LH surge & 24 to 36hrs before ovulation Measurement of ovulation doesnot confirm presence of ovulation Use of home LH kits not only provide accurate information to timing of ovulation,may also reduce stress Costs associated with infertility programs Consists of ovulation dipstick kits Effectively predicts ovulation in 70% of women

26. Dr.Sarma 28 THANK YOU