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Infertility ppt
- 1. Infertility DR KAVERI Associate Professor DEPT OF OBGY GIMS
- 2. DEFINITION • After one year of frequent, unprotected sexual intercourse there is no conception or maintenance of pregnancy • INCIDENCE : 15 – 30% couples
- 3. SUBFERTILITY • Inability to conceive after one year of regular unprotected intercourse in the absence of known reproductive pathology. • Peak monthly pregnancy rate ~ 30% • Cumulative rate in 1 year ~ 85% • Cumulative rate in 2 years ~ 95%
- 4. • FECUNDABILITY : probability that a cycle will result in pregnancy. • FECUNDITY : probability that a cycle will result in a live birth. • In a normal fertile couple - 20% to 30%
- 5. Types of Infertility • PRIMARY INFERTILITY: Patients who have never conceived • SECONDARY INFERTILITY : Previous pregnancies but failure to conceive subsequently
- 6. ETIOLOGY • Male factors: 30% • Female: 45% • Tubal: 20% • Ovulatory disorders: 25% • Uterine: 10% • Endometriosis: 5% • Unexplained:25% • Combined male and female: 40%
- 7. SPERMATOGENESIS • 74 days from spermatocyte stage • Transport 12-21 days
- 9. Causes of Male Infertility • 1. IDIOPATHIC (40-50%) • 2. HYPOTHALAMIC & PITUITARY DISORDERS (1-2%) Pre – Testicular • 3. PRIMARY GONADAL DISORDERS (30-40%) Testicular • 4. SPERM TRANSPORT DISORDERS (10- 20%) Post - Testicular
- 10. PRE – TESTICULAR CAUSES Hypothalamic & pituitary disorders (1-2%) CONGENITAL • Idiopathic isolated gonadotropin deficiency(M/C) • Kallmann syndrome • Single gene mutations • Multiorgan genetic disorders: PraderWilli syndrome Laurence Moon Beidl syndrome. ACQUIRED • • Hth & pit tumors • • Infilterative diseases • • Hyperprolactinemia • • Drugs • • Critical illness • • Chronic systemic illness • • Infections • • Obesity
- 11. TESTICULAR CAUSES Primary gonadal disorders (30-40%) • CONGENITAL • Klinefelter syndrome • Y chromosome deletions • Single gene mutations • Cryptorchidism • Varicoceles • Androgen insensitivity syndromes • 5 alpha reductase deficiency • ACQUIRED • Infection(mumps orchitis) • Drugs • Radiation • Gonadotoxins • Chronic illness • Hyperthermia • Immunologic disorders • Trauma • Torsion • Castration
- 12. Post Testicular causes SPERM TRANSPORT DISORDERS (10-20%) • • Epididymal obstruction or dysfunction • • Hypospadias • • CBAVD • • Infections • • Vasectomy, herniorraphy • • Kartagener syndrome • • Young syndrome • • Ejaculatory dysfunction
- 13. MALE INFERTILITY EVALUATION • ●History • ●Examination • ●Investigation • 1. Conventional Semen analyses • 2. Specialized Semen analysis • 3. Endocrine testing • 4. Genetic tests
- 14. HISTORY Focuses on causes of infertility. • Personal: Age, occupation, special habits • Present: Type of infertility, duration • Sexual: Frequency, erection, ejaculation, dysparunia, habits, libido.
- 15. History Past: • Medical: Chronic medical illness Infections: mumps orchitis, sinopulmonary symptoms, STI, and GUI (prostatitis) • Surgical: inguinal and scrotal areas such as vasectomy, orchiectomy, and herniorrhaphy • Trauma • Developmental: testicular descent, pubertal development, loss of body hair, or decrease in shaving frequency
- 16. History • Drugs and environmental exposures alcohol, radiation therapy, anabolic steroids, cytotoxic chemotherapy, drugs that cause hyperprolactinemia, exposure to toxic chemicals. • School performance : determine if he has a history of learning disabilities
- 17. Examination • General physical examination : general built , nutrition, skin & hair, sec sexual characteristics, habitus & breast development. • Examination of penis, location of urethral meatus • Palpation of testes & size • Presence & consistency of vas & epididymis • Digital rectal Examination
- 18. Semen analysis A. Macroscopic • 1. Delayed liquefaction • 2. Increased viscosity • 3. Semen volume • 4. pH B. Microscopy • 1. Agglutination • 2. Concentration • 3. Motility • 4. Morphology • 5. Round cells • 6. Leukocytes
- 19. Normal Semen Analysis Results (WHO) • Volume >2ml • pH 7-8 • Concentration >20 x 106/ml • Motility >50% forward & >25% with rapid linear progress • Morphology > 15% normal • Alive > 50% • Antisperm antibodies Negative • WCC < 1x106
- 20. • II. SPECIALIZED SEMEN ANALYSIS Not routinely performed used to determine the cause of male infertility • 1. Sperm autoantibodies • 2. Semen Fructose • 3. Semen culture • 4. Sperm function tests CASA SDNAF
- 21. Investigations • III. ENDOCRINE TESTS 1. Testosterone 2. LH and FSH 3. Prolactin • IV. GENETIC TESTS 1. Karyotyping 2. Y chromosome microdeletions 3. Cystic fibrosis conductance regulator (CFTR) gene mutation
- 22. Semen Analysis
- 23. Abnormalities of Semen Analysis • Azoospermia : Complete absence of sperm on std microscopic examination in ejaculate. • Oligospermia : sperm density < 20 million/ml.
- 24. • Asthenospermia : Poor sperm motility. • Teratospermia : > 70% abnormal morphology. • Necrospermia : dead sperm. • Leucocytospermia > 1million leucocytes/ml
- 25. Urologic evaluation • Physical examination • TRUS (transrectal usg for duct obstruction) • Transscrotal Usg • Renal Scan • Testis Biopsy in azoospermic men • Vasogram
- 26. MEDICAL TREATMENT Hypogonadotropic Hypogonadism: • Hyperprolactinoma- Dopamine agonists • Cong hypogonadotropic hypogonadism- hCG or exogenous testosterone • Adult onset hypogonadotropin hypogonadism- hCG 2000-5000 IU 3 times per week. Hypogonadotropin hypogonadism unrelated to cause- Portable programmable pulsatile infusion pump s/c
- 27. Eugonadotropin Hypogonadism • Severe oligospermia • Low Sr. testosterone • T/t by aromatase inhibitor (Testolactone 50- 100 mg BD or Anastrazole 1 mg OD)
- 28. Hypergonadotropic Hypogonadism • Insemination with donor sperm • IVF with ICSI with preliminary genetic evaluation Erectile dysfunction :Sildenafil- 25-100mg 1hr before intercourse
- 29. Retrograde Ejaculation- • Sympathomimetics, pseudoephidrine, ephedrine • IVF & IUI & ICSI Leucocytospermia- • Antibiotics (doxycycline, erythromycin, cotrimoxazole Idiopathic Male Infertility- • Androgen therapy • Exogenous FSH • Clomiphene citrate (25 mg)/Tamoxifen (20 mg)
- 30. SURGICAL TREATMENT 1. Vasovasostomy & vasoepididymostomy- In vasectomized men 2. Transurethral resection of the ejaculatory ducts- in men with Ejaculatory duct obstruction. 3. Varicocele repair- In men with varicoceles. 4. Orchipexy – In cryptorchidism 5. Vibratory stimulation & Electroejaculation – In neurological dysfunctions
- 31. 3-Reproductive Technique (ART) • I- Intrauterine Insemination (IUI) • II- IVF/ICSI
- 32. ARTIFICIAL INSEMINATION • Indications : • Oligospermia, • Asthenospermia, • Premature or retrograde ejaculation, • Sperm autoantibodies & cervical factors, • Unexplained infertility • Sex selection in genetic & chromosomal anomalies • Hypospadias • HIV positive
- 33. Types: • 1. IUI • 2. Intracervical • 3. Pericervical & Vaginal • 4. DIPI (Direct intraperitoneal insemination
- 34. Implementation and Collaborative Care • Sperm Washing for Intrauterine Insemination (IUI) – Ejaculate is centrifuged to concentrate sperm, which are then rinsed with saline to remove the seminal fluid – Sperm are again centrifuged, and then used for either IVF or Intrauterine artificial insemination
- 35. IUI
- 36. Implementation and Collaborative Care • Intrauterine Insemination (a form of artificial insemination) – Sperm are collected within 3 hours of colitus and are inserted via a catheter into the uterus – Donor sperm may be used – Identify of the sperm donor is kept confidential
- 37. Donor Sperm INDICATIONS : • 1. Azoospermia • 2. Immunological factors not correctable • 3. Genetic disease in husband
- 38. Female infertility • ovulatory dysfunction • tubal and peritoneal factors • cervical factors • Uterine factors • others • unexplained infertility
- 40. Ovarian disorders Ovulatory disorders: Infrequent ovulation (oligoovulation) or absent ovulation (anovulation) Oocyte aging: Ovarian cysts:
- 43. PCOS Rotterdam Criteria (2 out of 3) Menstrual irregularity due to anovulation or oligo-ovulation Evidence of clinical or biochemical hyperandrogenism Polycystic ovaries by US • presence of 12 or more follicles in each ovary measuring 2 to 9 mm in diameter and/or increased ovarian volume.
- 44. Ovarian failure Causes • 1. Idiopathic. • 2. Genetic. • 3. Autoimmune • 3. Viral/bacterial infection • 4. Pelvic surgery, chemotherapy • 5. Galactosemia
- 45. Tubal factors • Tubal disease and pelvic adhesions prevent normal transport of the oocyte and sperm through the fallopian tube. • PID • Severe endometriosis • Previous surgery or non-tubal infection (eg, appendicitis, inflammatory bowel disease), • Pelvic TB
- 47. Endometriosis
- 48. Uterine factors Impaired implantation, either mechanical or due to reduced endometrial receptivity, are the basis of uterine causes of infertility. Uterine leiomyomata:A meta-analysis showed that only leiomyomata with a submucosal or intracavitary component were associated with lower pregnancy and implantation rates.
- 49. Uterine anomalies; Uterine abnormalities are thought to cause infertility by interfering with normal implantation. Müllerian anomalies are a significant cause of (RPL), with the septate uterus associated with the poorest reproductive outcome . Other structural abnormalities endometrial polyps synechiae from prior pregnancy related curettage.
- 50. CERVICAL FACTORS Normal midcycle cervical mucus facilitates the transport of sperm. Congenital malformations and trauma to the cervix (including surgery) may result in stenosis and inability of the cervix to produce normal mucus, thereby impairing fertility.
- 51. UNEXPLAINED Unexplained infertility is the diagnosis given to couples after a thorough evaluation has not revealed a cause. Many cases of unexplained infertility may be due to small contributions from multiple factors.
- 52. History-General • Both couples should be present • Age • Previous pregnancies by each partner • Duration of infertility • Sexual history Frequency and timing of intercourse Use of lubricants Impotence, dyspareunia • Contraceptive history
- 53. History-Female • Previous female pelvic surgery • PID • Appendicitis • IUD use • Ectopic pregnancy history • Endometriosis • Leiomyoma
- 54. History • Irregular menses, amenorrhea, detailed menstrual history • Molimina • Vasomotor symptoms • Changes of hair growth, breast discharge • Stress • Weight changes • Exercise-drug –radiation -chemotherapy • Cervical and uterine surgery
- 55. Physical Exam-Female • Thyroid exam • BMI • Hair distribution • Galactorrhea • Scar in the abdomen • Pelvic masses • Uterosacral nodularity • Abdominopelvic tenderness • Uterine enlargement • Uterine mobility • Cervical abnormalities • Abnormal vaginal discharge
- 56. Investigations Assessment of ovulation • Basal body temperature • Urine LH kits • Mid luteal serum progesterone • Routine hormonal profile: FSH, LH,Prolactin,TSH • Endometrial biopsy • Serial pelvic Ultrasonography
- 58. • Evidence of ovulation: 1. Menstrual history of regular cycles. 2. Serum progesterone in the mid-luteal phase of their cycle (day 21 of a 28-day cycle) even if they have regular menstrual cycles. 3. Serum gonadotrophins ( FSH & LH) on Day2-3 especially in irregular periods. No role for basal body temperature
- 59. Ovarian reserve tests More important in >35 years old, suspected ovarian failure and to detect response to ovulation induction. • 1. Total antral follicle count. • 2. AMH of less than or equal to 5.4 pmol/l for a low response and greater than or equal to 25 pmol/l for a high response • 3. FSH greater than 8.9 IU/l for a low response and less than 4 IU/l for a high response.
- 61. Investigations of tubal factor • Hysterosalpingography (HSG) • Hysterosalpingo-contrast sonography(HyCoSy) • Laparoscopy with chromotubation • Hydrolaparoscopy. • Fluoroscopic/hysteroscopic- selective tubal cannulation. • Falloposcopy
- 62. Diagnostic Studies – Female • Hysterosalpingogram (HSG) – Detects uterine anomalies (septate, unicornate, bicornate) – Detects Tubal anomalies or blockage – Iodine-based radio-opaque dye is instilled through a catheter into the uterus and tubes to outline these structures and x-rays are taken to document findings
- 64. HSG
- 65. Diagnostic Studies – Female • Laparoscopy – General or epidual anesthesia – Abdomen is insufflated with carbon dioxide – One or more trochars are inserted into the peritoneum near the umbilicus & symphysis pubis – Laparoscope visualizes structures in the pelvis – Can perform certain surgical procedures
- 68. Assessment of the uterine cavity Modalities to assess the uterine cavity include • Saline Infusion Sono-hysterography (SIS) • Three dimensional sonography • Hysterosalpingography (HSG) • Hysteroscopy
- 69. Investigations NOT indicated in clinical practice • Serum antisperm antibody • Postcoital test • Sperm function test • Endometrial biopsy • Hysteroscopy • Ultrasound of endometrium
- 72. Treatment of female infertility General advice • folic acid whilst trying to conceive and during the first 12 wks of pregnancy to prevent neural tube defects • Reduce body weight in obese women • Stop smoking • Avoid excessive alcohol
- 73. Good health Free from illness eg thyroid, blood pressure, diabetes Avoid food fads Balanced diet Folic Acid Supplements
- 75. Management of Hypothalamic pituitary failure Amenorrhea or severe oligomenorrhea FSH & LH: low Prolactin: normal • 1. Reverse the life style factors: • Increase wt if BMI <19 • Moderating exercise if high levels of exercise. • Treat stress • 2. Gonadotrphins with LH activity or Pulsatile GnRH (pump)
- 76. Management of PCOS Weight reduction Drugs • Clomiphene citrate • Gonadotrophin releasing hormone • Gonadotrophin • Others: insulin sensitising agents (metformin) • Letrozole Surgery • ovarian drilling
- 77. Clomiphene Citrate (cc) • 1) Starting dose is 50 mg daily for 5 days, can be started b/t day 2- 6 of menses, • 2) Check for ovulation • 3) If there is ovulation, continue the same dose for 3-6 cycles, either with timed coitus or with IUI. • 4) No response, increase dose by 50 mg in each cycle, until a maximum of 150mg per day. • 5) If no response to the maximum dose, further increase is not effective
- 78. Gonadotrophin therapy In women with PCOD Aim: • Ripen follicles with repeated doses of FSH • Stimulate ovulation with injection of LH or hCG Drugs in use: • HMG– 75 IU FSH, 25-75 iu LH • Urofollitrophin—75 IU FSH n almost no LH • Recombinant FSH—75 IU FSH • hCG—1000-5000 IU hCG
- 80. Management of Resistant PCOS
- 81. Management of Tubal Factors Tubal surgery • microsurgical technique • laparotomy or laparoscopy • adhesiolysis, re-anastomosis, salpingostomy • In vitro fertilization and embryo transfer (IVF-ET)
- 82. Management of Uterine Factors Myomectomy indications
- 83. Management of Uterine Factors • Septate uterus Not increased among women with infertility compared with other women (2–3%). More common: RM or PTL. • Hysteroscopic metroplasty:
- 84. Management of Uterine Factors Intrauterine adhesions with amenorrhoea • hysteroscopic adhesiolysis
- 86. Assisted Reproductive Technologies (ART) • IVF-in vitro fertilization and embryo transfer • GIFT-gamete intrafallopian tube transfer • ZIFT-zygote intrafallopian tube transfer • ICSI - Intracytoplasmic sperm injection
- 87. INVITRO FERTILIZATION (IVF) Indications • - Severe tubal damage/ blockage. • - Bilateral salpingectomy. • - Endometriosis. • - Mild male infertility. • - Unexplained infertility. • - Immunologic infertility.. • Success rate: About 20-30%
- 88. Basic Steps in IVF • Ovary stimulation • Egg retrieval • Sperm retrieval-wash sperm • Fertilization • Embryo transfer • Progesterone
- 89. Drugs used for ovary stimulation • Clomiphene (clomid)-anti-estrogen • hMG (pergonal)-menopausal gonadotropin (FSH and LH) • FSH-(metrodin) • GnRH • GnRH agonists (lupron)-FSH/LH first promoted, then inhibited hCG-acts like LH
- 90. Egg retrieval
- 91. Sperm Retrieval Techniques • MESA – microsurgical epididymal sperm aspiration. • PESA – percutaneous epididymal sperm aspiration. • TESE – testicular sperm extraction.
- 92. • Gametes mixed for GIFT
- 93. GIFT
- 94. GIFT
- 95. ZIFT
- 96. ZIFT
- 98. ICSI
- 99. ICSI • Indication : (Male factors) • - Oligozoospermia. • - Asthenospermia. • - Teratozoospermia. • - Antisperm Ab. • - Fertilization failure after conventional IVF. • - Ejaculatory disorder
- 100. IVF Side Effects • Cysts on the ovaries • Multiple births • Ovarian Hyperstimulation • Risk of ovarian cancer
- 101. Alternatives to Childbirth • Adoption • Surrogate mothers • Frozen embryos • Egg donors • Frozen eggs • Cloning