1206-INFERTILITY

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1 Infertility 嘉義長庚藥劑科李振嘉藥師 2016/12/06 1

2 OUTLINE Definition of infertility Cause of ifertility Diagnosis of infertility Treatment Summary 2

3 Definition In the absence of contraception and at least one year of sexual life without pregnancy. In the statistics show that about 10-15% of couples will have infertility problems. 3

4 Primary infertility: -A couple who have never had child. Secondary infertility: -Once pregnant, but later for some reason can no longer be pregnant. 4

5 OUTLINE Definition of infertility Cause of ifertility Diagnosis of infertility Treatment Summary 5

6 In a World Health Organization (WHO) - Female factor(37%) - Male factor(8%) - Both male and female factor(35%) - The remaining couples had unexplained infertility or became pregnant during the study. 6

7 Female factor: Ovulatory disorders Cervical and uterine factors Tubal blockage Endometriosis Polycystic Ovary Syndrome (PCOS) 7

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9 AMH(Anti-Mullerian hormone) By the small ovarian follicle secretes, the number of small follicles,serum AMH concentration higher. AMH concentration is not affected by the menstrual cycle. Early detection of ovarian function decline. 9

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11 Endometriosis Ovulation disorders: -Endometriosis patients with ovulation difficulties and irregular menstrual problems. Intercourse pain Follicles can not rupture Fallopian tube delivery embryo competence disorder Luteal function deficiency 11

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14 Male factor: Semen abnormalities Testicular sperm production Sperm transport system abnormalities Sexual dysfunction 14

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16 OUTLINE Definition of infertility Cause of ifertility Diagnosis of infertility Treatment Summary 16

17 Diagnosis method Female: Basal body temperature measurement(bbt) Hormone detection ex:fsh, LH, Estradiol, Prolectin,Progesterone,AMH Ultrasound Hysterosalpingography(HSG) Hysteroscopy Laparoscopy 17

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19 Hysterosalpingography Trans-vaginal ultrasound 19

20 Hysteroscopy Laparoscopy 20

21 Diagnosis method Male: Basic semen analysis Hormone detection Microbiological aspects of the test Ultrasound examination Testicular sections 21

22 世界衛生組織 2010 新版精蟲檢測標準值 WHO 2010 Semen Analysis Criteria WHO 1999 ( 舊 ) WHO 2010 ( 新 ) 濃度 (Concentration) 2000 萬 1500 萬活動力 (Total motility) 50% 40% 精液容量 (Volume) 2mL 1.5mL 外觀型態 (Morphology) 30% normal forms 15% normal form 4% 22

23 OUTLINE Definition of infertility Cause of ifertility Diagnosis of infertility Treatment Summary 23

24 Treatment of infertility can be divided into three steps: First step: Promote ovulation Second step: Artificial insemination(aih) Third step: In vitro fertilization(ivf) 24

25 口服刺激排卵藥 Antiestrogen agent Clomiphene (50mg/tab)(Clomiphene 喜妊錠 ) - Increase the release of gonadotropin, causing the pituitary to secrete more FSH. - 對部分病人會改變子宮內膜厚度及降低子宮頸黏液可能降低療效 25

26 口服刺激排卵藥 - In the first 3-5 days of menstruation began to take 5 days. - Dose : 50mg/d - Side effect: Hot flushes, Breast tenderness, Nausea, Nomiting, Headache, Ovarian hyperstimulation 26

27 口服刺激排卵藥 Aromatase inhibitors Letrozole (2.5mg/f.c tab)(femara 復乳納膜衣 ) - Inhibition of estrogen production,reduse estrogen on hypothalamus negative feedback, increased pituitary secretion of FSH. - In the first 3-7 days of menstruation began to take 5 days. 27

28 口服刺激排卵藥 - Dose:2.5mg/d - Side effect: Gastrointestinal discomfort,weakness, Hot flashes, Headaches - The advantage is that there will be fewer follicles and lower estradiol, so the probability of multiple births less 28

29 Hypothalamus Clomiphene + GnRH Pituitary LH FSH Aromatase inhibitors Ovary Estrogen+Progesterone 29

30 Gonadotropin therapy Follicle stimulating hormone (FSH, 濾泡刺激素 ) - Promote the generation of mature follicles Luteinizing hormone(lh, 黃體刺激素 ) - Stimulate follicular development Human menopausal gonadotropins(hmg, 人類停經後性腺激素 ) Human chorionic gonadotropin(hcg, 人類絨毛膜性腺激素 ) 30

31 Gonadotropin therapy Low-dose, step up protocol to 75 iu/day, 7day - Ultrasonography and serum estradiol monitoring - Increments 成熟的濾泡一般是 of 37.5 iu 20mm then 以上 are, given 最小的在 at weekly 一般來說, 成熟的濾泡一般是 - Maximum of 225 iu/day Step-down protocol 最小的在 18mm 以上才正常 iu/day is started shortly after spontaneous or progesterone-induced bleedingeding - Dominant follicle (>10mm),the dose is then decreased to iu/day followed by a further decrease to 75 iu/day 31

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33 Gonadotropin therapy Gonal-F Menopur Pergoveris Elonva 33

34 Follitropin alfa recom. 75iu/vial(Gonal-F ) Anovulatory disorder: Usage: S.C - Initial: 75 iu daily; incremental dose adjustments of up to 37.5 iu may be considered after 14 days; further dose increases of the same magnitude can be made, if necessary, every 7 days (maximum dose: 300 iu daily). If response to follitropin is appropriate, hcg is given 1 day following the last dose. 34

35 Follitropin alfa recom. 75iu/vial(Gonal-F ) 針對接受試管嬰兒的婦女 : Usage: - Initiate therapy with follitropin alfa in the early follicular phase (cycle day 2 or day 3) at a dose of 150 iu daily, until sufficient follicular development is attained. - Consider adjustments to dose after 5 days based on the patient's response; adjust subsequent dosage every 3-5 days by iu additionally at each adjustment. Doses >450 iu daily are not recommended. 35

36 Follitropin alfa recom. 75iu/vial(Gonal-F ) Male: - 劑量應為 150 iu 每週投予三次, 配合 hcg 治療至少四個月 Side effect : Headache, ovarian cysts,injection site of the local reaction(pain, redness, swelling, irritation ), Ovarian hyperstimulation syndrome 36

37 Menotropins (Menopur )(FSH 75 iu + LH 75 iu) Usage: S.C or I.M Usage: - Initial: 225 iu once daily beginning on cycle day 2 or 3,Dose should be adjusted after 5 days based on ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels.(maximum daily dose: 450 iu) Once adequate follicular development is evident, hcg should be administered. 37

38 Menotropins (Menopur )(FSH 75 iu + LH 75 iu) Male: - 每週三次, 每次 1-2 瓶, 通常和 hcg 每週 3000 iu 的劑量分次合併注射一般要維持 10~12 週以上 Side effect: - For only: Rash; mild to moderate uncomplicated ovarian enlargement or ovarian cysts. - For only: Gynecomastia. 38

39 Follitropin alfa 150 iu+lutropin alfa 75 iu/pc (Pergoveris ) Usage: S.C Hypogonadotropic hypogonadism: - FSH 150 iu/lh 75 iu once daily. If an increase in FSH is necessary, dose may be adjusted in increments of FSH 37.5 to 75 iu every 7 to 14 days - Duration of stimulation in any one cycle may be extended up to 5 weeks Side effect: - Headache, abdominal pain, abdominal distension, abdominal discomfort, nausea, vomiting, diarrhoea, ovarian cysts, breast pain, pelvic pain, mild or moderate OHSS 39

40 Corifollitropinalfa100(150)mcg/0.5ml/syringe (Elonva ) Combination with gonadotropin-releasing hormone antagonist: 60 kg -100 mcg single injection during early follicular phase of menstrual cycle 60 kg -150 mcg single injection during early follicular phase of menstrual cycle 40

41 - Stimulation day 5 or 6, start gonadotropin-releasing hormone antagonist. - Stimulation day 8, give recombinant follicle stimulating hormone 150 international units daily until final oocyte maturation triggered (3 follicles of 17 mm or greater).

42 Gonadorelin-releasing hormone and analogues(gnrh analogues) GnRH agonist: Leuprolide(3.75mg/vial) (Depot leuplin) [X] - Stimulates the pituitary gland INDICATION: Prostatic carcinoma, Endometriosis. Dosage: - Endometriosis- Depot: SC, 3.75mg once a month. - 月經開始的第 1-5 天打第一針, 推薦治療期為 6 個月 - Side efect: Cardiac arrhythmias or palpitations; blurred vision; hot flashes ; nausea or vomiting; weight gain 42

43 GnRH antagonist: Cetrorelix (0.25mg/vial) (Cetrotide 欣得泰 ) [X] - 抑制 (Luteinizing hormone releasing hormone, LHRH) INDICATION: Female infertility Dosage: - Singie: SC, 3 mg administered when serum estradiol concentration indicates an appropriate stimulation response, usually on cycle Day 7. If human chorionic gonadotropin (HCG) was not administered within 4 days after cetrorelix, 0.25 mg cetrorelix should be administered QD until the day of HCG administration. - Multiple: SC, 0.25mg qd starting on the morning or evening of Day 5. 43

44 Other agent: Dopamine agonists: - Inhibition of prolactin secretion in the anterior horn of the hypothalamus Bromocriptine (2.5mg/cap) ) (Volbro 歐普酪 ) [B] INDICATION: Parkinsonism Secondary amenorrhea, galactorrhea, male hypogonadism, and infertility due to hyperprolactinemia Acromegaly Pituitary prolactinomas Dosage: Initial: mg qhs 44

45 Cabergoline (Dostinex) (0.5mg/tab) [B] INDICATION: Hyperprolactinemic disorders, Pituitary prolactinomas Dosage: mg,biw In accordance with patient's serum prolactin level, dosage may in increments of 0.25mg, up to 1mg biw Side effect : Abdominal pain, Nausea, dry mouth, postural hypotension, dizziness, hallucinations, delusions, drowsiness or tiredness: 45

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47 Other agent: Metformin: - 抑制肝臟製造與釋出葡萄糖, 以及增加細胞對葡萄糖的利用, 達到降低胰島素的目的 - 多囊性卵巢症候群 (PCOS) 的患者有一部份有胰島素阻抗性, 血中胰島素升高, 間接導致排卵異常, 因此近年來開始有人用 Metformin 來治療多囊性卵巢症候群 - Dosage: 500mg, TID - 一般服用期間約為六個月 47

48 Artificial insemination(aih) 48

49 In vitro fertilization(ivf) 49

50 In vitro fertilization(ivf) Insemination Intracytoplasmic Sperm Injection(ICSI) 50

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52 OUTLINE Definition of infertility Cause of ifertility Diagnosis of infertility Treatment Summary 52

53 Summary In the absence of contraception and at least one year of sexual life without pregnancy. - Primary infertility: - Secondary infertility: Cause - Female factor - Male factor - Both male and female factor - Unknow 53

54 Summary First step: Promote ovulation - Oral ovulation drugs - Gonadotropin therapy Second step: Artificial insemination(aih) Third step: In vitro fertilization(ivf) 病患本身必須保持心靈健康和平常心去面對, 才能做好準備面對到來的新生命 54

55 Thanks for your attention 55

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97017626 O O 2 3 4 5 22 22 23 25 35 38 39 45 46 1 intrauterine insemination IUI 202 IUI a 24 IUI b 24 IUI c hcg 36 IUI d hcg 24 48 IUI 202 262 30 2 1 27 1 14.9% 11.5% a 122 151 13.9%, 11.3% b 42 46 2.38%,