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Infertility Dr. Sura Findakly OB/GYN specialist College of medicine AL-Mustansiriyah university Classification Primary infertility: couples who had no previous conception. Secondary infertility: couples who had previous conception. Causes of female infertility WHO c...

Infertility Dr. Sura Findakly OB/GYN specialist College of medicine AL-Mustansiriyah university Classification Primary infertility: couples who had no previous conception. Secondary infertility: couples who had previous conception. Causes of female infertility WHO classification of ovulation disorders Group I ovulation disorders (hypogonadotrophic hypogonadal anovulation) are caused by the hypothalamic pituitary failure,e,g Kalman syndrome. Around 10 % of women. Group II ovulation disorders (normo-gonadotropic, normo-gonadal anovulation) are caused by the hypothalamic-pituitary-ovarian axis dysfunctions. polycystic ovary syndrome and hyperprolactinemic amenorrhoea.Around 85% of women Group III ovulation disorders (hyper-gonadotrophic, hypogonadal anovulation) are caused by ovarian failure. Around 5% of women Evaluation of a couple with infertility History Female partner Age : the fertility decreases with age, quality of egg also affected and causes loss of the pregnancy. Type of infertility; primary or secondary infertility (including history of previous marriage, any previous fertility investigation or treatment). Gynecological history including menstrual history (menarche ,cyclicity ,dysmenorrhea ,any history of amenorrhea or menorrhagia , intermenstrual bleeding), history of PID or STD , history of prior contraceptive use , history of pregnancy complication(in case of secondary infertility ) like miscarriage ,retained placenta, fetal anomalies, history of abnormal Pap smears(particularly if a woman underwent cervical conization which could impact cervical mucus quality & cervical competence). Medical history: including any symptoms of hyperprolactinemia or thyroid disease , symptoms of androgen excess such as acne or hirsutism may point to the presence of polycystic ovarian syndrome or much less commonly congenital adrenal hyperplasia , H.T, DM surgical history; focus on pelvic & abdominal surgeries ,e.g.ruptured appendicitis or diverticulitis suspicion for the pelvic adhesive disease or tubal obstruction or both, rupture ectopic pregnancy Drug history : including drugs that cause hyperprolactinemia, prior chemotherapy or pelvic irradiation may suggest the presence of ovarian failure. NSAIDs that may adversely affect ovulation, corticosteroid. Sexual history: coital frequency & timing including knowledge of the fertile period, dyspareunia, post coital bleeding. Social history including life style like eating habits as BMI more than 25 or less than 17 affect GnRH & gonadotropin secretion smoking , alcohol consumption. Monitoring of ovulation: presence of regular menstruation would suggest that ovulation is occurring, probable ovulation is also suggested by the presence of Mittelschmerz sign which is mid cycle pain associated with ovulation, breast tenderness , acne, & mood changes, dysmenorrhea. Basal Body Temperature( BBT): progesterone, BBT may rise by 0.5 - 1 C after ovulation so serial measurement at morning during periovulatory phase of the cycle is required. Cervical mucus change under influence of estrogen ,cervical mucus become thin ,clear & stretchable. EXAMINATION General: height, weight, BMI, fat & hair distribution, acanthosis nigricans, presence of acne & galactorrhoea,thyroid enlargement.Abdominal: any mass or tenderness.Pelvic: assess normality of vulva,vagina(looking for infection or vaginal septa ,endometriotic deposits).cervix (check for the presence of cervical polyps).Uterine size, shape, position, mobility & tenderness.perform PAP smear if indicated. History Male partner Type of infertility, any fertility in the previous relationship(secondary infertility),previous fertility investigation & treatment. Medical :STD, epididymitis ,mumps orchitis ,testicular maldescent ,smoking & alcohol abuse ,recurrent UTI. Surgical: herniorrhaphy, testicular injury, torsion, orchidopexy, vasectomy or reversal, varicocele Occupational: exposure to toxic substance (including chemicals &radiation),time away from home through work. Sexual: onset of puberty,coital habbits,ejaculatory problem(premature ejaculation erectile dysfunction specially if associated with beard growth may suggest decrease testosterone level, assess libido,assess the knowledge of fertile period. Examination: General: height, weight, BMI, fat & hair distribution, evidence of hypoandrogenism or gynecomastia. Groin: examine for inguinal hernia or any inguinal mass e.g. ectopic testicle. Genitalia:site of testicles in the scrotum & measure their volume ( normally 20 mL),palpate epididymis for nodularity or tenderness (chronic infection), check for the presence & normality of vas deference (bilateral absence may indicate cystic fibrosis).Penis:for any structural abnormality e.g. hypospadias. Tests of ovulation Semen fluid analysis Serum Progesterone : measure in Parameters midluteal phase.Sample taken at 21 of 28 day cycle. Serial check is Normal value required if the cycle is longer , shorter ▪ Volume 1.5 ml or more cycle length require earlier assessment before 21 (7 day after ▪ PH 7.2–7.8 ovulation ).Serum progesterone in ▪ Sperm conc. ≥15× 106/ml excess of 30 nmol/L 7 days after ovulation indicate ovulation. ▪ Total sperm ≥39 × 106/ml Ovulation predictor kits :mid-cycle LH ▪ Motility ≥ 32% prog. surge in urine. motility Ultrasound: used to track follicular development, rupture & corpus ▪ Morphology 4% normal luteum formation. ▪ Viability 58% or more live Endometrium biopsy: day 25 of the cycle show sign of ovulation. ▪ White blood cells Blood test: LH , FSH , Prolactin , Fewer than 1 ×106/ml thyroid function test. Tests for tubal patency 1) X-ray hysterosalpingography 2) Laparoscopy & dye hydrotubation 3) Hysterosalpingo-contrast sonography 4) Falloposcopy 5) Salpingoscopy 1- Hysterosalpingography It is radiographic evaluation of uterus and fallopian tubes under Fluoroscopic guidance Time: it should be done during follicular phase of cycle, but not during menstruation Indications Contraindications Infertility to assess 1. Suspected pregnancy tubal patency 2. Active vaginal bleeding Recurrent 3. Acute pelvic infection miscarriage 4. Recent dilation and curettage (congenital 5. Immediate pre and post anomalies of menstrual phase uterus). 6. Tubal or uterine surgery within 6 Postoperative weeks evaluation following 7. Contrast sensitivity (a) tubal ligation,(b) Complication reversal of tubal 1. Pain ligation. 2. Infection To prove tubal occlusion after 3. Vasovagal episode insertion of 4. Pregnancy irradiation sterilization 5. Allergic reaction microinsert. 6. Uterine perforation Unilateral tubal block bilateral tubal block Bilateral distal tubal blockage 2) Laparoscopy & dye hydrotubation: A colored dye is injected through the cervix while carrying out laparoscopic inspection of the pelvis. -Assessing tubal patency -Direct visualization of pelvis to identify any pathology like adhesion, fibroid, endometriosis, ovarian cyst that may be relevant to infertility It needs GA & it is hazards, also there is risk of injury to bowel , bladder & blood vessels. 3) Hysterosalpingo-contrast sonography : Carried as outpatient procedure, a small balloon catheter is inserted in uterine cavity through the cervix -It allows assessment of tubal patency -assessment of uterine cavity e.g. uterine polyp. -need ultrasound skills & the instillation of fluid may be uncomfortable. 4) Falloposcopy: Achieve access to tube per vagina. 5) Salpingoscopy: The tube is cannulated through fimbria during laparoscopy or laparotomy. laparoscopy laparoscopy Unilateral hydrosalpinx 2 2 1 HyCoSy 3 Assessment of uterine cavity Hysteroscopy: Also done as outpatient procedure, any uterine malformation, fibroid, endometrial polyps, adhesion can be identified & treated. Post coital test: Has limited prognostic value & is rarely used today it involves the assessment of the periovulatry cervical mucus & sperm in sample obtained from female partner 6-10 hours after coitu Tubal disease treatment: The aim is to restore the normal anatomy of the tubes. The success rate depends on the severity, location of the damage as well as the skills of the surgeon.e.g. tuboplasty If the fallopian tubes are beyond repair one must consider in vitro fertilization Surgical treatments (laparoscopic, Hysteroscopic) Lysis of adhesions Septoplasty Tuboplasty Myomectomy General: Management giving patients life style advice regarding conception peri-conception folic acid up to 12 weeks gestation as this reduces the risk of neural tube defects; and also offer women rubella screening & rubella vaccination to avoid congenital rubella syndrome. Optimum weight( BMI 20-25). Treatment of ovulation disorder Type I ▪ If underweight achieve BMI of 20. ▪ Gonadotrophin. ▪ Pulsatile GnRH. ▪ If hyperprolactinaemia , give dopamine agonist e.g. bromocriptine or cabergoline. ▪ IVF. Type II the commonest cause is PCOS, it needs ovulation induction by:- 1. Reduction of body weight by 5-10% of body weight may restore ovulation. 2. Anti-estrogen treatment e.g. clomiphene (50 mg/day for day 2-6 of the cycle is the usual starting dose.U/S monitoring is recommended.In woman who do not respond to initial dose ,then the dose is increased in 50 mg increment in subsequent cycles to a maximum of 150 mg/day.Usually a maximum of 12 treatment cycles 3. Gonadotrophins :It is used in women who fail to conceive with clomiphene.A low –dose step up regime is used with starting dose of FSH, the dose. 4. hCG is used to trigger ovulation when adequate response is achieved ;S.F. multiple pregnancy & ovulation hyperstimulation syndrome Type III Ova donation. Assisted reproductive technique Intrauterine insemination is where a prepared sample of sperm (normally produced by masturbation) is inseminated into the uterine cavity at the appropriate time of the patient’s menstrual cycle. Approximately two weeks later a pregnancy test is performed to see if the cycle has been successful. Indications ▪ Mild male Factor(mild oligozoospermia) ▪ Sever hypospadias ▪ Asthenospermia ▪ Ejaculatory problems(retrograde ejaculation) ▪ Cervical problems(stenosis, hostility) ▪ Ovulatory disorders ▪ Mild endometriosis ▪ To optimize the use of donor sperm ▪ Unexplained infertility Complications(in stimulated IUI) ▪ multiple pregnancy ▪ Ovarian hyperstimulation syndrome ▪ Ca ovary (if stimulation exceed 12 cycles) 1 2 In vitro fertilization (IVF). IVF is where the mature oocytes surgically removed from the ovary and then fertilized with sperm in the laboratory. Indications ❑ Severe endometriosis ❑ Moderate male factor(moderate oligozoospermia) ❑ Unsuccessful IUI ❑ Cryopreservation of oocyte or embryo for IVF Prior to chemotherapy ❑ Severe tubal disease – tubal blockage ❑ Premature ovarian failure(donation oocyte and IVF) ❑ Unexplained infertility Complications ▪ multiple pregnancy ▪ Ectopic pregnancy ▪ Ovarian hyperstimulation syndrome ▪ Ca ovary (if stimulation exceed 12 cycles) A typical IVF-Embryo transfer cycle 1. Initial consultation 2. Pituitary down-regulation 3. Superovulation ovarian stimulation 4. Ovulation trigger with hCG trigger 5. Oocyte collection 6. Fertilization (Insemination of oocytes or intracytoplasmic sperm injection ICSI) 7. Embryo transfer 8. Luteal phase support 9. Pregnancy test Intracytoplasmic sperm injection(ICSI) A type of fertilization procedure in which a sperm is injected directly into an egg to achieve fertilization. Indications Sever oligozoospermia. Sever oligo-astheno-teratozoospermia. Failed IVF. -Oocyte collection - ICSI -Oocyte insemination - Embryo transfer Treatment of male infertility Male fertility depends on sperm quality rather than the absolute number of sperm present. ❑ Men with hypogonadotrophic hypogonadism are treated with exogenous gonadotrophins and hCG to restore testicular volume and spermatogenesis. ❑ Hormonal therapy is, however, ineffective at restoring sperm production or function in men with idiopathic oligospermia. ❑ intrauterine insemination IUI with ovarian stimulation may be an appropriate treatment. ❑ Alternatively , couples may choose to proceed to IVF with intracytoplasmic sperm injection. ❑ Men with obstructive azoospermia can be offered corrective surgery or sperm aspiration followed by IVF with ICSI treatment. ❑ Men with hypergonadotrophic-hypogonadism(testicular failure) Although 25 per cent of men with abnormal sperm parameters have a varicocele , there is no evidence that surgical ligation improves fertility. ▪ Alternatively , couples may choose to proceed to IVF with intracytoplasmic sperm injection. ❑ Men with obstructive azoospermia can be offered corrective surgery or sperm aspiration followed by IVF with ICSI treatment. ❑ Men with hypergonadotrophic- hypogonadism(testicular failure) Although 25 per cent of men with abnormal sperm parameters have a varicocele , there is no evidence that surgical ligation improves fertility. Ovarian hyperstimulationsyndrome(OHSS) It is a condition that occurs when there is excessive stimulation of the ovaries by drugs that are used to induce ovulation e.g. clomiphene , gonadotrophins. Risk factors Women under 30 years , thin and slim one. Low BMI, PCOS, History of OHSS Use of GnRH agonists in combination with gonadotrophins Use of exogenous hCG either as ovulatory trigger or luteal support Endogenous surge of hCG due to pregnancy Large NO. of follicles (9000 p mol/l) Rapid increase in estradiol levels (more than 75% increase from previous day) Classification of OHSS Severity Clinical findings Ultrasound picture Mild Abdominal bloating with some pain Ovaries< 8 cm Nausea ,vomiting & increased abdominal discomfort Ovarian size Moderate Evidence of ascites 8 – 12 cm Severe Clinical ascites (with or without hydrothorax) with Ovaries45% ,WBC > 15000/ml & liver dysfunction Critical Tense ascites , PCV > 55% ,WBC > 25000/ ml ,oliguria (with Ovaries >12 cm raised S. creatinine ), renal failure ,thromboembolic Gross ascites complication , Adult respiratory Distress Syndrome may be seen. Investigations ▪ Full blood count including PCV & WBC, platelet.Haematocrit ▪ Renal function test and serum electrolytes ▪ 24 hours protein in urine ▪ liver function tests(elevated enzymes & decrease in serum albumin). ▪ Coagulation profile(s.fibrinogen , antithrombin,PT,PTT) ▪ U/S which shows ovarian enlargement & multiple cysts formation, ascites. Other investigations according to clinical presentation ▪ Blood gases ▪ D. Dimer ▪ ECG and ECHO for pericardial effusion ▪ Chest x-ray for plural effusion ▪ CT angiogram and V/Q Scan in suspected PTE. In mild cases In severe cases Management ▪ The treatment is supportive & Hospital admission is required monitoring of the patient while ▪ Monitoring of vital sign ,urine output ,fluid balance & awaiting spontaneous resolution. abdominal girth , weight , Analgesia: paracetamol, ▪ Pain relief (paracetamol & codeine ,avoid NSAIDS can opioids),avoid NSAIDs, cause renal impairment. ▪ Thromboprophylaxis(LMWH,ab ove knee stocking) Encourage fluid intake to ▪ progesterone luteal support can thirst, to avoid fluid over load. be continued & termination of Avoid extreme exercise and pregnancy rarely needed. sexual intercourse. Luteal phase support. Patient should be seen every 2- 3 days with regular blood tests to assess response or changing to sever form. Thank you

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infertility ovulation disorders female reproductive health medicine
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