Ovarian Stimulation in IUI- Overview

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Ovarian Stimulation in IUI- Overview

• Dr. Jyoti Bhaskar
• MD MRCOG
• Director Lifecare IVF

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Rationale for COH in IUI

• Increasing the number of eggs available for
  fertilisation
• Overcoming subtle defects in ovulatory function
  and luteal phase.

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Aim of COH

• Recruiting multiple follicles
• Control timing of ovulation
• Prevention of premature LH surge
• To time the insemination
• Increase the pregnancy rate

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Optimum Ovarian Stimulation for IUI

• 2 3 follicles with Ø 18 20 mm.
• Endometrium ? 8 mm thick trilaminar.
• IUI between Cycle D13 and D16, 36-40 hrs. from
  HCG inj.

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Classification

• WHO
• I - Hypothalamic pituitary failure
  (Hypogonadotrophic hypogonadism)
• Kallmans, Sheehans, anorexia
• II - Hypothalamic pituitary dysfunction (PCOS)
• III Ovulatory Failure Hypergonadotrophic
  hypogonadism, Turners, autoimmune, mumps, RT, CT

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Drugs for Ovarian Stimulation

• Clomiphene Citrate, Tamoxifen
• Gonadotrophins
• HMG
• Highly purified urinary FSH
• Recombinant. FSH
• GnRH Agonist/ Antagonist

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CLOMIPHENE CITRATE

• Most widely
• Simple to use,
• Minimal side effects,
• Cost effective

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CLOMIPHENE CITRATE ( SERM)
Binds
HYPOTHALAMUS ER
GnRH
Blocks ER
Pituitary
FSH
Cervix
Vagina
OVARY
Endometrium
Folliculogenesis
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DOSAGE

• Single dose -- together
• Monitor Cycle with USG
• If ovulation confirmed maintain same dose
• Max to 150 mg

Starting Dose 100mg day 2 onwards for 5 days
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CC CHECK

• Evaluation of the patient on Day 2
• Previous cycles
• TVS ET , AFC and cysts
• Review reports of FSH, LH if available

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CC FAILURE ( 40) No Pregnancy 3 CYCLES OF CC
WITH OVULATION AND TIMED INTERCOURSE
2 CYCLES OF CC WITH IUI
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CC RESISTANCE (20) 3 CYCLES OF CC NO
OVULATION
COST , PTS CHOICE COUNSELLING
Wt loss, extended CC, adjuvants metformin,
dexamethasone
CC GONADOTROPHINS
GONADOTROPHINS
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Antioestrogenic Effect

• Thin Endometrium
• Poor cervical Mucus

Start early in cycle Day 2 or Day 1 Add
oestradiol valearate from day 8/9 Use all
gonadotrophin cycle
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Gonadotrophins - Indications

• CC Resistance
• CC Failure
• WHO 1

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Choice of Gonadotrophins

• HMG
• Highly purified Urinary HMG/FSH
• Recombinant. FSH

Day 2 LH/FSH
FSH WHO group1
LH PCOS
FSH
HMG
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DOSE

• BMI
• Ovarian reserve
• Age
• Cause of Infertility
• Dose needed in previous cycle

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Complications

• Multifetal pregnancy
• OHSS - Life threatening

Monitoring Experience Strict protocols
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Protocols

• CC only with TI or IUI
• CC FSH or HMG with IUI
• Gonadotrophin only
• Conventional regime
• Gn. Low dose step-up protocol
• Gn. step-down protocol
• 4. Gonadotrophin with GnRH antag

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B LONG F ONCE DAILY ALL THROUGH OUT THE CYCLE
UPT 18 days after IUI/Ovulation
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Oocyte mature
38 hrs
Clomiphene 100 mg day2 for 5 days
Gonadotrophin stimulation
Leading follicle gt 18mm
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Gonadotrophin Regimens
Chronic Low dose Step up regimen
150 IU
112.5 IU
hCG
75 IU
37.5 IU
Days
7
14
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Step down
112.5 IU
150 IU
hCG
75 IU
Foll. ? 10 mm
Conventional Regime
75-150 U daily
hCG
2
6
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Foll. ? 16mm
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Gonadotrophins with Antagonists
15-20 cycles with Gonadotrophins have premature
LH surge
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Advantages of Antagonist Protocol

• Helps avoid IUI at weekends
• Prevents premature surge
• Compared to agonist simple and inexpensive
• Lower rates of OHSS

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• Anti-oestrogens
• Cost effective but less effective when compared
  to gonadotrophins.
• Do not prevent multiple pregnancies
• Have anti-oestrogenic effect on the endometrium
• Gonadotrophins
• Most effective drugs for IUI
• Low dose protocols (50 to 75 IU per day) are
  advised
• Pregnancy rates do not seem to differ
  significantly from pregnancy rates with high dose
  regimens (gt 75 IU per day) whereas the changes to
  encounter negative effects from ovarian
  stimulation, such as the risk of multiples and
  the risk of OHSS might be higher with high dose
  protocols.

The Cochrane Library 2011, Issue 6 Cantineau AEP,
Cohlen BJ
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• GnRH-agonists
• There seems to be no role in IUI programs
• Increase costs
• Increase multiples without increasing the
  probability of conception
• Urinary gonadotrophins versus Recombinant
  products
• There is no significant difference
• GnRH-antagonists
• Whether or not are going to play a role in mild
  ovarian hyperstimulation/IUI programs needs to be
  determined in future trials.
• Letrozole
• There is no convincing evidence that Letrozole
  is superior to clomiphene citrate and therefore
  the cost should be taken into account when using
  anti-oestrogens.

The Cochrane Library 2011, Issue 6 Cantineau AEP,
Cohlen BJ
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Ovarian stimulation protocols(anti-oestrogens,
gonadotrophins with and without GnRH
agonists/antagonists)for intrauterine
insemination (IUI) in women with subfertility
(Review) The Cochrane Library 2011, Issue 6
Cantineau AEP, Cohlen BJ
Gonadotrophins might be the most effective drugs
with IUI Low dose protocols are advised No
studies using CC gonadotrophins
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• There is evidence that IUI with OH increases the
  live birth rate compared to IUI alone.
• The likelihood of pregnancy was also increased
  for treatment with IUI compared to TI both in
  stimulated cycles.
• There is insufficient data on multiple
  pregnancies and other adverse events for
  treatment with OH.
• Therefore, couples should be fully informed about
  the risks of IUI and OH as well as alternative
  treatment options.

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Conclusion

• Ovarian Stimulation protocol
• Simple
• Cost Effective
• Minimal side effects
• Best success rates

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Conclusion

• Choice depends on doctors expertise and patient
  selection and choice
• Gonadotrophin only protocol offers the best
  success rate

TIME TO MOVE ON TO TOTAL GONADOTROPHIN CYCLE
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Thank you