infertility causes and management in female

Infertility causes and management

1. Infertility- definition Inability of a couple to conceive after one year of regular, unprotected sexual intercourse

2. Infertility- Incidence Infertility affects 10-15 % of couples In normal young couples- Fecundity 25% conceive after one month 70% conceive after six months 90% conceive by one year

3. Infertility- Risk factors Risk factors Women’s age- ↑age → ↓ fecundity Others: Smoking, illicit drugs, occupational and environmental exposures

4. Infertility- Types Primary infertility Infertility without previous pregnancy Secondary infertility Infertility following a previous pregnancy 2 years after a previous pregnancy without contraception including lactation.

5. 35% 50% 5% 10% Male Combined Unexplained Female Infertility- Causes

6. Infertility- Causes Male factors (35%) Female factors (50%) Ovulation (20%) Tubal & peritoneal factor (20%) Uterine & Cervical factor (10%)

7. Infertility- Causes Unexplained infertility (10- 15%) Combined factors (5%) Male & female factors Sexual disorders Immunological factors

8. Role of female in fertility Ovulation and functioning CL Transport of ovum from ovarian surface to the tube- normal peritoneum & Fimbria Transport of the ovum and the zygot through the tube to the uterus Implantation of the blastocyst in the uterus Transport of sperms through cervix & vagina Female causes

9. Ovulatory disorders According to WHO classification - Group 1: Hypothalamic pituitary failure - Group II: Hypothalamic- pituitary dysfunction Group III- Ovarian failure Hyperprolactinemic GnRH + + - - - - - - High E2 LH FSH Hypothalamus Low P4 Low E2 + - - Ovary P p i i t t u u i t i t a a r y ry + O o v v a a r r y y

10. WHO type I- hypothalamic-pituitary failure Criteria Hypogonadotrophic hypogonadism ↓ FSH, LH, E Normal prolactin level Presents with amenorrhea Progesterone challenge test is –ve Ovulatory disorders

11. WHO type I- hypothalamic-pituitary failure Causes Anorexia nervosa Exercise-related Post- pill amenorrhea Pituitary infarction (Sheehan's syndrome) Kallman’s syndrome Hypothyroidism -Idiopathic

12. WHO type II- Hypothalamic pituitary dysfunction Criteria Most common imbalanced Gn H (High LH/FSH ratio- >2) Normal estrogen or hyperestrogenemia Chronic anovulation oligomenorrhia Causes - Polycystic ovarian syndrome (PCOS)

13. WHO type III- ovarian failure Criteria Hypergonadotrophic hypogonadism ↑ FSH, LH, ↓ E Causes Premature and age-related ovarian failure Resistant ovarian syndrome Turner syndrome (XO)

14. Symptoms suggestive of ovulation Regular cycle Spasmodic dysmenorrhea Premenstrual tension syndrome Mid- cycle pain (mettelschmerz pain) Mid- cycle discharge & spotting Diagnosis of ovulatory disorders

15. symptoms suggestive ovulatory factor Irregular period Headache, visual changes, galactorrhea- hyperprolactinemia (pituitary tumor) Palpitation, heat/cold intolerance-thyroid dysfunction Hirsutism-hyperandrogenemia Diagnosis of ovulatory disorders

16. Symptoms suggestive ovulatory factor Excessive exercise- hypothalamic- pit failure Advanced age, hot flushes, vaginal dryness- peri- menopause, menopause, POF Ovulatory disorders- cont.

17. Examination suggestive ovulatory factors PCOS- Obesity, hirsutism may be detected Breast examination- galactorrhea Signs of - Hypo or hyperthyroidism - Turner syndrome Underweight- hypothalamic factors Diagnosis of ovulatory disorders

18. Detection of ovulation Special tests Basal body temperature (BBT) Ovulation Sudden thermal shift for 10 days Anovulation No thermal shift LPD Thermal shift <10 d pregnancy

19. Serial cervical mucous study Profuse with +ve ferning & +ve spinnbarkeit tests Tests turns –ve in 2 nd half of the cycle Detection of ovulation

20. Serial TVS (folliculometry) To detect pre-ovulatory mature follicle (Graffian follicle 17-20mm) Detection of ovulation

21. Hormonal assay Serum progesterone at D21 of the cycle Level > 10 ng/ml- ovulation Level 3-10 ng/ml- LPD Level < 3 ng/ml- anovulation Detection of ovulation

22. Serial LH in urine- to detect LH surge- 36 hrs before ovulation S.prolactin, TFT Serial vaginal smear Endometrial biopsy Detection of ovulation

23. Treatment of ovulatory disorders WHO type I Gaining weight- BMI >20 kg/m2 Pulsatile administration of GnRH agonists WHO type II Weight loss, exercise Induction of ovulation

24. 1. Medical treatment Clomiphene Citrate Non- steroidal drugs similar to estrogen It blocks ER in the hypothalamus & pit. Glands → ↑ LH, FSH → follicle development Given form D2- D6 of the cycle Induction of ovulation

25. Side effect Anti E effect Hot flushes, vaginal dryness, etc Headache & blurred vision(retinal vein thrombosis/sudden loss of vision: rare) Thinning of the endometrium Thickening of cervical mucous induction of ovulation

26. Induction of ovulation GIT upset, abdominal bloating Breast discomfort ↑ risk of twins & abortion Ovarian hyperstimulaiton syndrome (OHSS) Ovulation is induced in 80% of cases Pregnancy rate is 35- 40% ??????? 20- 25% show no response- Resistant

27. Induction of ovulation Human menopausal gonadotrophin HMG Prepared from urine of menopausal women Used in combination with CC or alone Dose: ampoule of 75 IU LH/ 75 IU FSH/ IM Side effect Expensive, painful OHSS Multiple pregnancy

28. Purified urinary FSH Recombinant FSH GnRH analogue (agonist) Pit. suppression by Down-regulation of Gn R → ↓ FSH, LH followed by OI using HMG or FSH Given as daily nasal spray or SC injections Given in cases of resistant PCO, ART Induction of ovulation

29. Human chorionic gonadotrophin HCG Prepared from the urine of the pregnant women 10.000 IU/IM give to resemble LH peak Used after stimulation of follicular growth by CC or HMG to induce ovum maturation Induction of ovulation

30. Others Tamoxifen, non-steroidal aromatase inhibitor- (letrozole) Insulin sensitizer- Metformine (PCO) Bromocriptin, Cabergoline: hyperprolactinemia Dexamethasone- PCO to ↓ adrenal androgens Thyroxine- hypothyroidism Induction of ovulation

31. Induction of ovulation 2. Surgical treatment Ovarian wedge resection (laparoscopy)

32. Laparoscopic ovarian drilling in PCO Induction of ovulation

33. Tubal & peritoneal factors Most common cause of 2ry infertility 1. Infection Pelvic inflammatory disease (PID) Gonococcal, chlamydia, TB Block of the lumen of the fallopian tube Peritubal adhesions- kinking of the tubes Previous pelvic peritonitis- ruptured appendix

34. Surgery Previous pelvic operation Previous ectopic pregnancy, C/S Previous gynecological surgery Cornual fibroid Endometriosis Congenital- hypoplasia, aplasia Functional- tubal spasm Tubal & peritoneal factors

35. Diagnosis History Pelvic pain- salpingitis, endometriosis h/o pelvic or abdominal operation h/o ectopic pregnancy or tubal surgery Examination Tender adnexal mass- salpingitis Limited mobility of uterus & ovaries Enodmetriotic nodules in US ligament Tubal & peritoneal factors

36. Tests for tubal patency Hysterosalpingography (HSG) Saline infusion sonography (SIS) Laparoscopy + hysteroscopy Tubal & peritoneal factors

37. HSG

38. SIS

39. Laparosco py

40. Treatment Tuboplasty?? Treatment of endometriosis Hydrotubation- insufflations of the tubes Assisted reproductive technique ART Tubal factors

41. Uterine factors Causes Congenital- aplasia, hypoplasia, septate, bicurnuate uterus Uterine surgery Endometritis & Asherman’s syndrome Endometrial polyp or fibroids Prolapse & retroverted uterus Refractory endometrium

42. Diagnosis History h/o 1ry amenorrhea- congenital cause Oligomenorrhea or recurrent abortion- congenital cause h/o repeated curettage or puerperial sepsis- Asherman’s syndrome Menorrhagia- uterine fibroids or polyp Uterine factors

43. Examination Small or absent uterus Failure to pass uterine sound Symmetrical enlargement of the uterus Investigations USS HSG, SIS Hysteroscopy, Endometrial biopsy Uterine factors

44. Uterine factors Treatment Lysis of adhesions, E therapy Myomectomy, polypectomy Correction of malformation- Metroplasty Antibiotics for endometritis

45. Cervical factors Causes Congenital stenosis Trauma to the cervix Conization or cauterization of the cx Obstetric trauma Chronic cervicitis- hostile cx mucus Cervical fibroids- distortion of cx canal Immunological- Antisperm antibodies

46. Investigations Quality of cervical mucous at ovulation Post- coital test Sperm penetrations test Culture & sensitivity- infe ction Cervical factors

47. Treatment Treatment of infections Cervical dilatation, myomectomy Antisperm antibodies - corticosteroids - IUI Cervical factors

48. Role of male in fertility Spermatogenesis by testis is stimulated by FSH from pituitary G Transport of sperms from the testis to exterior by epididimis, vas deference, ejaculatory ducts through the prostate and urethra Deposition of sperm in the vagina via coitus Male factors

49. Causes Defect in spermatogenesis Congenital- undescended testis Exposure to radiation, chemicals, smoking Infection- Orchitis (mumps, TB) Chromosomal- klinefelter’s syndrome (47 XXY) Hormonal- hypothyroidism - hyperprolactinemia Immunological - Drugs Male factors

50. Bilateral obstruction of the vas deference Congenital- CBAVD (cystic fibrosis) Ligation during hernia repair Infection- gonorrhea Failure of deposition of sperm Severe hypospadius Impotence Retrograde ejaculation Idiopathic Male factors

51. Diagnosis History Age, occupation, Smoking Past h/o infection, operation Past medical history Sexual history Drug history Male factors

52. General examination Klinefelter syndrome - tall Gynacomastia Small testis Endocrine abnormalities- hypothyroidism Male factors

53. Local examination Penile deformities Testis- detect undescended or atrophic testis Varicocele PR- detect prostate abnormalities Male factors

54. Investigation Semen analysis Doppler US- varicocele Hormonal assay FSH Androgens, prolactin, thryoid H. Male factors

55. Male factors Investigation Testicular biopsy Chromosomal analysis Immunological studies Microbiology of the semen

56. Semen analysis (WHO criteria) Liquefies within 30 min of collection Volume: 2- 5 ml - pH: alkaline (≥7.2) Count: ≥ 20 million/ml Motility: ≥ 25% grade A (rapid progressive) ≥ 50% grade A+B Normal forms: ≥ 30% Viability: ≥ 75% viable WBC: <1 million/ml Male factors

57. Azoospermia- (absence of sperms) Oligozoospermia- (sperm conc. <20 m/ml) Asthenozoospermia- impaired motility- (Kartgener’s syndrome) Teratozospermia: > 70% abnormal sperm morphology on microscopy Male factors

58. Male factors Treatment General measures Changes in lifestyle Stopping smoking Stopping or reducing alcohol consumption Exercise, reduce wt Avoid tight underwear Avoid chemical and radiological exposure

59. Medical: Bromocriptin/Cabergoline Thyroxin Antibiotics Multivitamins- Vit A, E, C, l- arginine, l- carnitine, Co-enyme Q10 Clomiphene citrate or hMG, hCG Male factors

60. Surgical treatment Varicocele ligations Correct the obstruction to vas deference Ejaculatory failure ART (Assisted Reproductive Technique) using surgical sperm retrieval from testis or epididymis Male factors

61. Immunological factors Presence of Ag- Ab reaction In Male: Antisperm Abs- serum, seminal fluid, sperm Post- trauma, surgery- testis or duct sys, infections. In female: Auto Abs against CL, Ovum, Blastocyst Cross Abs against sperm in Cx mucous

62. Immunological factors Diagnosis Last and least to think about Anti sperm Abs tests Agglutination tests Immobilization test Immunoflorescent tests Immunobeads tests Treatment corticosteroids, ART

63. Is diagnosed when routine investigation including semen analysis, tubal evaluation, tests of ovulation yield normal results. A period of 3 years is generally accepted before active intervention is considered Unexplained infertility

64. Unexplained infertility Treatment Clomiphene citrate IUI with or without superovulation IVF

65. Assisted Reproductive Technology ART

66. ART Treatments for Infertility Intrauterine insemination (IUI) IVF with embryo transfer Intra- cytoplasmic sperm injection (ICSI) Cryopreservation Gamete intra- fallopian transfer (GIFT) Zygote intra- fallopian transfer (ZIFT)

67. Intrauterine insemination IUI

68. Intrauterine insemination IUI Indications Unexplained infertility Mildly impaired semen analysis Sexual dysfunction Ovulatory disorders Mild endometriosis

69. Intrauterine insemination IUI Technique Induction of ovulation- follicle of ≥18mm HCG injections- final maturation of ovum 34- 36 hrs later- processed semen is injected into the uterine cavity using special catheter

70. IUI

71. Indications Severe tubal disease-blockage Severe endometriosis Moderate male factor Unexplained infertility Unsuccessful IUI IVF with Embryo Transfer IVF- ET

72. IVF with Embryo Transfer IVF- ET Controlled ovarian hyperstimulation (COH) Ovum aspiration (pickup) 34- 36 hrs after HCG injection Sperm preparation Combining sperm and ovum in a petri dish with culture medium, incubated for 2–5 days

73. TVOR or ovum pickup

74. IVF with Embryo Transfer IVF- ET If fertilization and cleavage occurs, embryos are graded and the best chosen. ET- at 8- cell stage of Day 2 embryos ET- at blastocyst stage of D5 embryo

75. Indicatio n: Severe male factor Poor or total non- fertilization from previous IVF cycles PGD Intra- cytoplasmic Sperm Injection (ICSI)

76. Intra- cytoplasmic Sperm Injection (ICSI) A single normal sperm is injected directly into the cytoplasm of the oocyte under microscope Increases probability of fertilization

77. ICSI microscope and micromanipulator

78. Sperm Oocyte Pronuclear stage (fertilization) 24 hrs after ovum pickup

79. 2- cell stage End of 24hrs 4- cell stage D2 embryo 8- cell stage D3 embryo Morula Expanded blastocyst Hatched blastocyst

80. Cryopreservation Sperm or embryos are preserved by freezing for replacement in subsequent cycles

81. Gamete Intra-fallopian Transfer (GIFT) Ovum retrieved via laparoscopy Ovum and sperm placed in same catheter Injected directly into the fallopian tube via laparoscopy Embryo travels through the fallopian tube to the uterus for implantation

82. Zygote Intra-fallopian Transfer (ZIFT) Combines techniques used in IVF and GIFT Ovum are placed in a petri dish with sperm If fertilization occurs, the zygote: Is injected into fallopian tube Travels through tube to uterus Implants in uterus

83. complications of ART OHSS Multiple pregnancy Ectopic pregnancy Complications of TVOR