infertility treatment related to pcos
DESCRIPTION
Infertility treatment related to PCOSTRANSCRIPT
INFERTILITY TREATMENT
RELATED TO PCOS The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2008
Prof Aboubakr Elnashar Benha university Hospital, Egypt
Treatment modalities
Lifestyle Modifications
Clomiphene Citrate Insulin Sensitizing Agents Gonadotrophins
Laparoscopic Ovarian Drilling IVF Ovulation Induction and IUI
Aboubakr Elnashar
Lifestyle Modifications
Obesity:
adversely affects reproduction {anovulation,
pregnancy loss and late-pregnancy complications}.
within PCOS: failure of infertility tt.
Weight loss:
prior to infertility tt
improves ovulation rates
limited data that it improves fecundity or lowers pregnancy
complications.
Aboubakr Elnashar
lifestyle modifications: 1st line tt of obesity in PCOS. Caloric restriction increased physical activity •The ideal amount of weight loss: unknown 5% decrease of B W
Aboubakr Elnashar
Clomiphene Citrate first choice for induction of ovulation in most
anovulatory women with PCOS.
Selection of patients for CC:
body weight/BMI
female age
other infertility factors.
The starting dose: 50 mg/d (for 5 days) maximum dose: 150 mg/d.
Aboubakr Elnashar
Monitoring:
US or P is not mandatory to ensure good outcome.
Conception rate:
up to 22%/cycle in those women ovulating on CC.
Aboubakr Elnashar
Aromatase inhibitors
Further studies to demonstrate efficacy & safety
Mechanism
1. Release the pituitary/hypothalamic axis from the
estrogenic negative feedback, increase Gnt secretion,
stimulate ovarian follicle development
2. locally in the ovary: increase the follicular sensitivity to FSH
Aboubakr Elnashar
Insulin Sensitizing Agents
Metformin
Restricted to those with glucose intolerance.
Alone: less effective than CC
Added to CC: no advantage
Aboubakr Elnashar
DIAGNOSIS OF INSULIN RESISTANCE
1. BMI: > 30 K/m2 is almost always IR
2. Waist to hip ratio: >0.85.
3. Waist cir.: >100 cm
4. Acanthosis nigricans (grey-brown velvety discoloration on neck, axilla or groin).
5. Numerous achrochordons (skin tags)
6. Fasting insulin: normal levels are variable 10-20 u/ml.
7. Fasting glucose insulin ratio < 4.5.
Aboubakr Elnashar
Continuing during pregnancy:
should be left to obstetricians&
based on a careful evaluation of
risks& benefits.
Recommended 2nd -line TT
should CC fail to result in
pregnancy:
Gnt or LOD.
Aboubakr Elnashar
Gonadotrophins:
Chronic low-dose
• Starting dose: 37.5 IU
• Duration of starting dose:14 d
• The weekly dose increment: reduced from 100% to
50% or 37.5 IU
:Marked dec in OHSS.
The duration: should not exceed 6 ovulatory cycles.
Aboubakr Elnashar
0 14 21 28 35
75 iu 112.5 iu
150 iu
187.5 iu
225 iu
Days
7
37.5 iu
½ Amp.
One Amp.
42 49
2 Amp.
3 Amp.
White et al. J Clin Endocrinol Metab 1996;81:3821–4 Aboubakr Elnashar
Monitoring
I. US
-Baseline:
-Serial
Documentation of all follicles >10 mm {predict the risk of
multiple pregnancies}.
Cycle cancellation
>3 follicles ≥16 mm
>2 follicles ≥16 mm or
>1 follicle ≥16 mm& 2 additional follicles ≥14 mm (ASRM,
ESGRE, 2008)
Aboubakr Elnashar
II. E2 levels: •Used to
cancel cycles (due to over- or under-response)
adjust the dose of Gnt •Caution:
rapidly rising or >2500 pg/ml (ASRM, 2006).
<1000 pg/ml
Aboubakr Elnashar
Overall, ovulation induction (representing
the CC, Gnt paradigm) is reported to be
highly effective with a cumulative
singleton live birth rate of 72%.
Aboubakr Elnashar
Laparoscopic Ovarian drilling
An alternative to Gnt for CC-RPCOS.
1. No risk of OHSS or
high-order multiples.
2. Intensive monitoring is not required
3. Single tt using existing equipment
Not be offered for non-fertility indications.
Aboubakr Elnashar
Risks:
1. risk of laparoscopy
2. adhesion
3. destruction of normal ovarian tissue.
To decrease risk:
1. Minimal damage to the ovaries.
2. Irrigation
3. trained personnel.
LOD is usually effective in <50% of women and
additional ovulation induction is required under those
circumstances.
Aboubakr Elnashar
IVF Recommended 3rd-line treatment {effective in women
with PCOS}.
IVF is a reasonable option, {number of
multiple pregnancies can be kept to a
minimum by transferring small numbers of
embryos}. The optimal stimulation protocol is still under debate: further RCTs
comparing FSH stimulation protocols with use of GnRHa Vs. GnRHant are required
PR in women with& without PCOS are similar: implantation is not compromised in PCOS.
The increase in the cycle cancellation rate in women with PCOS:
1. absent or limited ovarian response or
2. increased OHSS.
Aboubakr Elnashar
Ovulation Induction and IUI Indicated:
1. Male factor
2. PCOS who failed to conceive despite successful induction of ovulation.
Aboubakr Elnashar
Overall Conclusions
Evaluation of women with presumed PCOS desiring pregnancy should exclude any other health issues in the woman or infertility problems in the couple.
Before any intervention is initiated, preconceptional counselling should be provided emphasizing the importance of life style, especially weight reduction and exercise in overweight women, smoking and alcohol consumption.
The recommended first-line treatment for ovulation induction remains the anti-estrogen CC.
Aboubakr Elnashar
•Recommended second-line intervention should CC fail to result in pregnancy is either exogenous Gnt or LOD. •Both have distinct advantages and drawbacks. Choice should be made on an individual basis. •The use of exogenous gonadotrophins is associated with increased chances for multiple pregnancy and intense monitoring of ovarian response is therefore required. •LOD is usually effective in <50% of women and additional ovulation induction is required under those circumstances.
Aboubakr Elnashar
•Overall, ovulation induction (representing the CC, gonadotrophin paradigm) is reported to be highly effective with a cumulative singleton live birth rate of 72%. •Recommended third-line treatment is IVF, because this treatment is effective in women with PCOS. Data concerning the use of single ET in (young) women with PCOS undergoing IVF, significantly reducing chances of multiple pregnancies, are awaited.
Aboubakr Elnashar
•More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. •Such approaches may result in deviation from the above mentioned first-, second- or third-line ovulation strategies in well-defined subsets of patients.
Aboubakr Elnashar
•Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. •Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. •Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.
Aboubakr Elnashar
GnRHa with Gnt: not justified: 1. The significantly higher OHSS 2. Risk of multiple pregnancies 3. Inconvenience 4. Cost 5. Absence of documented increases in pregnancy success
Aboubakr Elnashar
