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Ovulation Induction: When to Go and When to Stop

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Andrew Murray

on 10 August 2013

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Transcript of Ovulation Induction: When to Go and When to Stop

Ovulation Induction:
When to Go and When to Stop?

Recommendations
Lifestyle Modification
Clomiphene (?+Metformin) x9 max
Laparoscopic Ovarian Drilling

OI with FSH
IVF

What are we treating?
Generalist
Subspecialist
No One Size Fits All Approach
Ovulation Induction as
Fertility Treatment
Anovulation

Unexplained Infertility
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
Cancer Risk?
Rossing et al NEJM 1994
Efficacy.. How Long?
Kousta 1997
Cumulative Rise in preg rate up to 6 cycles
Modest Rise thereafter
Increased Cancer risk >12 cycles
Clomiphene
Monitoring
Simple
Check Luteal Progesterone >30

Simple Monitored
Single Scan (not too many follicles)

Fully tracked
Multiple scans, Estrogen and LH monitoring
Possible "Triggering"
Complexity

Expense
Metformin
Not Pregnant

Improved BMI
6-12 Cycles CC
+/- Metformin

Now What?


group one
hypothalamic pituitary failure or hypogonadotrophic hypogonadism 10%

group two
hypothalamic pituitary dysfunction or eugonadotrophic 85%

group three
ovarian failure or hypergonadotropic hypogonadism 5%
WHO
Classification Ovulation
Disorders
PCOS Consensus
ASRM/ESHRE
CC resistance
Aim for weight reduction before commencing Clomiphene
BMI >35
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
LOD Settings
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
40W
4 seconds
4 punctures
4mm
Which are You?
OI with Gonadotrophins

or

IVF
Criteria for Funding

9 cycles CC +/- Metformin
or
Not Preg 12 months after LOD

BMI <32
Non smoker
Metformin
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
Ovulation
Metformin vs placebo 3.88 (CI 2.25 to 6.69)

Metformin vs M/CC 4.41 (CI 2.37 to 8.22)
Pregnancy
Placebo vs M/CC 4.40 (CI 1.96 to 9.85)
BUT...
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