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Ovulation Induction: When to Go and When to Stop
Transcript of Ovulation Induction: When to Go and When to Stop
When to Go and When to Stop?
Clomiphene (?+Metformin) x9 max
Laparoscopic Ovarian Drilling
OI with FSH
What are we treating?
No One Size Fits All Approach
Ovulation Induction as
Clomiphene citrate for
unexplained subfertility in women
Cochrane Review 2010
Hughes E, Brown J, Collins JJ, Vanderkerchove P
A U T H O R S ’ C O N C L U S I O N S
No evidence that clomiphene citrate has an effect on pregnancy rate in women with unexplained subfertility.
Further research is unlikely to change the ﬁndings and therefore clomiphene would not be recommended as a treatment for unexplained subfertility.
There is unlikely to be further evidence which would change these ﬁndings and, therefore, this review will not be updated.
At least 2 out of 3:
oligo-ovulation or anovulation;
clinical or biochemical signs of hyperandrogenism
polycystic ovaries ultrasound scanning
Exclusion of other causes
First-line treatment for anovulatory women.
Anti-oestrogen and competes for receptor binding sites with endogenous oestrogens
Increases number of follicles recruited
Dose is 50 to 100 mg (maximum of 250 mg) for
5 days usually commencing day 2 to 5
Multiple Pregnancy Risk 8-10%
Clomiphene resistance common 15% to 40% of women with PCOS
(Kousta 1997; Pritts 2002; Wolf 2000).
Resistance = Anovulatory with 150 mg dose of clomiphene citrate (NICE 2004)
Resistance more likely with high BMI
A nomogram to predict the probability of live birth
after clomiphene citrate induction of ovulation
in normogonadotropic oligoamenorrheic infertility
Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. Fert Stert 2002
Rossing et al NEJM 1994
Efficacy.. How Long?
Cumulative Rise in preg rate up to 6 cycles
Modest Rise thereafter
Increased Cancer risk >12 cycles
Check Luteal Progesterone >30
Single Scan (not too many follicles)
Multiple scans, Estrogen and LH monitoring
6-12 Cycles CC
hypothalamic pituitary failure or hypogonadotrophic hypogonadism 10%
hypothalamic pituitary dysfunction or eugonadotrophic 85%
ovarian failure or hypergonadotropic hypogonadism 5%
Aim for weight reduction before commencing Clomiphene
Laparoscopic Ovarian Diathermy/Drilling
Reduces stromal production of androgens
Increases non-steroidal factors for response to FSH
Increases IGF-1 which increases FSH receptor recruitment
Laparoscopic ovarian diathermy in women with polycystic ovarian syndrome: a retrospective study on the influence of the amount of energy used on the outcome S.A.K. Amer1, T.C. Li and I.D. Cooke Human Reproduction 2001
Rule of 4's
Which are You?
OI with Gonadotrophins
Criteria for Funding
9 cycles CC +/- Metformin
Not Preg 12 months after LOD
What does the evidence say?
Lord JM, Flight IHK, Norman RJ.
Insulin sensitising drugs vs placebo
for polycystic ovary syndrome
Cochrane Database of Systematic Reviews 2003
Metformin vs placebo 3.88 (CI 2.25 to 6.69)
Metformin vs M/CC 4.41 (CI 2.37 to 8.22)
Placebo vs M/CC 4.40 (CI 1.96 to 9.85)