Insulin sensitizing agents use in pregnancy and as therapy in PCOS - PowerPoint PPT Presentation

Loading...

PPT – Insulin sensitizing agents use in pregnancy and as therapy in PCOS PowerPoint presentation | free to download - id: 56d652-NGQyN



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Insulin sensitizing agents use in pregnancy and as therapy in PCOS

Description:

Insulin sensitizing agents use in pregnancy and as therapy in PCOS J. SERNA MD. PhD. IVI Madrid * * * * * * * * * * * * * * * * * * * * * * * 1st trimester Jakubowicz ... – PowerPoint PPT presentation

Number of Views:68
Avg rating:3.0/5.0
Slides: 43
Provided by: Jos458
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Insulin sensitizing agents use in pregnancy and as therapy in PCOS


1
Insulin sensitizing agents use in pregnancy and
as therapy in PCOS
  • J. SERNA MD. PhD.
  • IVI Madrid

2
TREAT WHAT?
Treatment Options
Imparied
Diet/lifestyle Metformin
Weight/Metabolic
Cyclic progesterone OCP
Dysfunctional bleeding
Metformin Clomiphene Letrozole Gonadotropins Ovari
an cautery
Infertility
OCP antiandrogen (spironolactone, flutamide,
finasteride) GnRH agonists
Skin
3
Type II anovulatory patients treatment options
  • Diet and exercise
  • Clomiphene citrate, Tamoxiphene
  • Aromatase Inhibitors
  • Insulin-Sensitizing Agents
  • Gonadotropins
  • FIV-ICSI /- IVM
  • Ovarian drilling

4
TREAT WHAT?
Treatment Options
Imparied
ISA
Weight/Metabolic
ISA
Dysfunctional bleeding
ISA
Infertility
ISA
Skin
5
(No Transcript)
6
CLOMIPHENE INDUCTION OF OVULATION IN PCOS
  • Bad prognostic factors
  • BMI gt31
  • Increased androgens
  • Amenorrhea
  • Older patients
  • Alternatives/associations
  • Metformin if IR
  • hCG
  • Glucocorticoids
  • Gonadotropins
  • Ovarian drilling
  • Non wanted effects
  • Cervical mucus, endometrium ??
  • Vascular side effects (11) visual side effects
    (2)
  • MP 7, OHSS, SAB ??

7
BMI
8
Insulin-Sensitizing Agents
  • a-Glucosidasa Inhibitors
  • Sulfonilureas
  • Methiglinides
  • Biguanides
  • Thiazolidindiones

9
(No Transcript)
10
(No Transcript)
11
PREGANACY WANTED
12
Therapeutical Scheme for PCOS Ovulation
Aromatase inhibitors??
Drilling???
13
(No Transcript)
14
Ovulation Induction vs. Ovarian Stimulation
Ovarian Stimulation
Ovulation Induction
Women with anovulation
Women ovulating
Restore oocyte production
Increase oocyte production
Monofollicular cycle
Polyfollicular cycle
15
Main purpose of ovulation induction
16
Ovulation and pregnancy
OHSS Multiple Pregnancy
Anovulation
Normal Ovary
Polycystic Ovary
17
  • OVULATION INDUCTION
  • Two mechanisms

DIRECT ACTION
INDIRECT ACTION
x
Clomiphene
GnRH
-
Estrogens
Gonadotropins
x
Aromatase inhibitors ? Decrease androstenedione
conversion to estrogens
18
Chance of ovulation and of a live birth after CC
Imani B. Fertil Steril 2001.
19
Baillargeon et al. 2004
20
Baillargeon et al. 2004
21
Baillargeon et al. 2004
22
  • Induces ovulation 6 to 8 folds
  • Decreases Serum Testosterone
  • Metformin, but not Rosiglitazone, improves HOMA
    IS
  • Rosiglitazone improves ovulation despite no
    significant improvements in insulin parameters

23
Metformin vs No Treatment vs. CC etaanalysis
24
209 CC 208 Metformin 6 months of
treatment 209 CCMetformin
626 patients
CC 22 Metformin 7 CCMetformin26
6 0 3
Multiple pregnancy
Live birth rate
First-trimester pregnancy loss did NOT differ
among the groups
25
CONCLUSIONS CC is gt to metformin in achieving
live birth in PCOS, although multiple birth is a
complication. No advantage of the combination
therapy over the CC
Independently of treatment, BMI lt 30 had a
higher rate of live births Ovulation rate was
higher in the combination group
26
METFORMIN IVF
27
METFORMINA FSH vs FSH Fedorsäck (2003)
  • 17 PCOS IR women
  • ? 2 cycles with and without metformin
  • BMI 32,0 kg/m2
  • Metf. ? do not decreases FSH units needed
  • Metf. ? more oocytes were retrieved

28
METFORMINA FSH vs FSH SOLO Kjotrod (2004 )
  • RCT double-blinded, placebo-controlled
  • 73 patients random. (BMIgtlt28kg /m2 )
  • Placebo/metf. 1000mg /day during 16 weeks

29
METFORMINA FSH vs FSH SOLO Kjotrod (2004 )
  • Duration of stimulation
  • Estradiol hCG day
  • Oocyte number fertilization rate
  • Embryo quality
  • Pregnancy rate

SIGNIFICANT DIFFERENCES ONLY IN PCOS BMIlt 28?
Clinical Pregnancy Rate
30
METFORMIN PREGNANCY
31
Rationale
  • Is it recommended to continue with metformin
    during pregnancy?
  • How long?
  • Which doses?
  • Which is the safety profile?

32
SAB, GD
  • PCOS patients do have an increased abortion rate
  • Jakubowicz ------------- 42
  • Glueck ------------- 39-73
  • Wang ------------- 25
  • PCOS patients do have an increased incidence of
    gestational diabetes
  • 46 risk

33
  • Risk factors
  • Hyperinsulinemia, Insulin Resistance
  • Hyperandrogenemia
  • Obesity
  • High PAI-Fas levels inducing hypofibrinolysis
  • Hyperhomocysteinemia

34
1st trimester
  • Jakubowicz et al, JCEM 2002
  • Retrospective study in patients with PCOS

35
1st trimester
  • Jakubowicz et al, JCEM 2002
  • Retrospective study in patients with PCOS

36
1st trimester
  • Glueck et al
  • Decreased SAB rate

37
Gestational Diabetes
  • Pregnancy induces a physiologic
    insulin-resistance increasing insulin needs
  • PCOS women do have a 46 risk for GD

38
Gestational Diabetes
  • Glueck et al
  • Decreased GD incidence.
  • Fertil Steril, 2002 Hum Reprod, 2002
  • Hum Reprod, 2004
  • Metformin diet
  • Previous and During Pregnancy Weight Reduction
  • Weight
  • Insulin, Insulin resistance, Testosterone
  • Decreased Risk of GD

39
Safety Profile
  • FDA group B
  • Either animal-reproduction studies have not
    shown a fetal risk but there are no controlled
    studies in women, or animal studies have shown an
    adverse effect not confirmed by controlled
    studies in women
  • Breast-feeding Hale et al, Diabetologia,2002
  • Mean doses 1500 mg/day
  • Mean concentration in babies 0,28
  • lt 10 dosage allowed

40
Metformin Pregnancy
  • Small studies non-controlled and short duration
  • Different Bias
  • Most of the obese patients non controlled for
    hyperinsulinemia

41
CONCLUSIONS
42
CONCLUSIONS
43
Thank you
About PowerShow.com