Drugs In OVULATION INDUCTION ILOs By the end

Drugs In OVULATION INDUCTION ILOs By the end of this lecture you will be able to: Recall how ovulation occurs and specify its hormonal regulation Recognize causes and types of female infertility Classify ovulation inducing drugs in relevance to the existing deficits Expand on the pharmacology of each group with respect to

Follicular Phase Primordial Pry 2/3 -7 d Recruitment Gn-independent Sec 13 cycles / year between puberty & menopause A Fertile; ovulates � 400 in life Selection Gn-responsive Little estrogen Preantral Antral LH > FSH SURGE X OVULATION INFERTILITY Graffian Follicle 12 -14 d Follicular Phase 7/8 -12 d Dominance=Maturatio n High estrogen Hormone-dependent

INFERTILITY A condition characterized by a reduction in ability to reproduce or to achieve conception Ø 1/3 attributed to women. Ø 1/3 attributed to male factors Ø 1/3 both or unexplained Endometriosi Tubal causes, s blockage or damage Fibroid s Polycystic Ovarian Syndrome Most common cause of female infertility Failure of Ovulation Miscarriage Common cause of female infertility

Ovulation Induction Clomiphene Tamoxifen Gn. RH-H agonists Leuprolin Goserelin D 2 R Agonists Bromocrepti ne GONADOTROP HINS HMGs; Menotropin HCGs; Pregnyl OVARIAN SYNDROME to �body weight & �response to ovulation induction drugs Ø Conception remote, no place for Hypothalamus � Gn. RH � Anterior Pituitary � (-) FSH / LH � (-) Ovary � Estrogen Progestins Normogonadotrophic � Ovarian METFORMIN; IN POLYCYSTIC Hypogonadotropic � Hypothalamo-pituitary ANTIESTRO GENS SERMs; Hyperprolactinaemia Hypergonadotrophic

ANTIESTROG ENS SER Ms Selective Estrogen Receptor Modulators [SERMs] �compete with estrogen on estrogen receptors in the nucleus Doing so they act as antagonists or partial agonists depending on how they bind & the different target tissue of action. In the hypothalamus & pituitary they have ANTAGONISTIC ACTION

SER Ms ØOn hypothalamus; � negative feed back of endogenous estrogen on hypothalamus�pulse � Gn. RH ��

Clomiphene given � 50 mg/d for 5 days from 5 th day of the cycle to the 10 th day. If no response give 100 mg for 5 days again from 5 th to 10 th day The drug can be repeated not more than 6 cycles. ADR s CLOMIPHENE ANTIESTROG cont Coitus every other. ENS day Clomiphene 50 -100 mg/d 5 days Method of administration 5 days 7 days SER Ms Progesterone LH FSH 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Menses 1. Hot Flushes & breast 5. Skin rashes tenderness 6. Fatigue 2. Gastric upset (nausea and 7. Weight gain vomiting) 8. Hair loss (reversible) 3. Visual disturbances N. B. �incidence of multiple ovulation �twins in (reversible)

2. TAMOXIFE Is similar & alternative to clomiphene N But differ in being Non Steroidal ANTIESTROG ENS SER Ms ØUsed in palliative treatment of hormone-dependent / estrogen receptor- positive advanced breast cancer ØBut why clomiphene not used in such cases of cancer brea

[FSH & GONADOTROP HINS LH] Are naturally produced by the pituitary gland For therapeutic use, extracted forms are available as; 1. Human Menopausal Gonadotrophins (h. MG )�extracted from postmenopausal urine �contains LH & FSH � MENOTROPIN 2. Human Chorionic Gonadotrophins (h. CG) extracted from urine of pregnant women � contains mainly LH) � PREGNYL N. B. Now new available preparations by recombinant technology Mechanis m ØPreparations of FSH � act on ovary directly, Given sequentially stimulating growth & maturation of Graafian Follicle(s) ØPreparations of LH � act just to induce Indication ovulation ØStimulation & induction of ovulation in infertility 2 ndry to gonadotropin

GONADOTROP HINS [FSH & Method of LH] administration h. MG is given i. m or subcut. every day starting at day 2 -3 Success rate for inducing ovulation is usually >75 % of cycle for 10 days followed by h. CG on (10 th - 12 th day) for OVUM RETRIEVAL within 36 hrs. When we indicate: §intrauterine insemination §or intercourse ADR s FSH containing preparations; Fever stimulation) 20%) Ovarian enlargement (hyper Multiple Pregnancy (approx.

Gn. R H LEUPROL IN GOSEREL IN Mechanis native-Gh RH Gn. RHAgonist m Native Gn. RH is naturally produced by hypothalamus in a pulsatile manner. It is triggered when the negative feedback inhibition of ovarian hormones is lost by the end of the cycle. This activates FSH release from pituitary that stimulate growth and maturation of ova early during the follicular phase of the cycle. It also mediates estrogen induced LH surge that triggers ovulation. Gn. RH-Agonists �bind to the receptors & mimic the native hormones provided it is given PULSATILE

Gn. RHAgonist If PULSATILE � Mimic native Gn. RH Intranasal, injectable & implant formulations Pulsati le LEUPRO LIN GOSERE LIN Gn. RHAgonist If CONTINOUS�Gn. R Block Gn. RH Receptors H In cancer (prostate & breast) & other long term indications as precocious Continuou puberty, endometriosis & s fibroids FSH & LH Growth maturation & rupture GONADAL ACTIVATI

Gn. R Use H LEUPRO Øs In OVULATION INDUCTION per se Given in hypothalmic amenorrhea (Gn. RH deficient)LIN �S. C. GOSERE pulsatile(drip) (1– 10 µg / 60 – 120 min) ��Gn. Hs release LIN Start from day 2 -3 of cycle up to day 10 In ASSISTED REPRODUCTION is part of a protocol for OVUM RETRIEVAL Ø OVUM RETRIEV AL After 36 hrs AD Rs ØGIT disturbances, abdominal pain, nausea…. etc ØHeadache ØHypoestrogenism on long term use � �Hot flashes �� Libido �Osteoporosis �Vaginal bleeding �Rarely ovarian hyperstimulation �(ovaries swell & enlarge)

D 2 R BROMOCREP TINE Agonists Is an ergot derivative. Mechanis D 2 R Agonists m bind to dopamine receptors Bromocreptin e in anterior pituitary �-ve PRL secretion Indication s ØFemale infertility 2 ndry to hyperprolactinaemia ( hypogonadotrophic) ADR s Ø GIT disturbances; nausea, Hyperprolactinaemi a No Ovulation