Ovarian

Factor

Infertility

Aboubakr

Elnashar

Benha University

Hospital, Egypt ABOUBAKR ELNASHAR

CONTENTS I. EVALUATION

TYPES OF ANOVULATION

INVESTIGATIONS

II. TREATMENT

TREATMENT OF ANOVULATION

TYPES OF OVARIAN STIMULATION

DRUGS FOR OVARIAN STIMULATION

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TYPES OF ANOVULATION

% Type Hormonal profile

5-10%

WHO type I

(Hypogonadotropic

Hypoestrogenic)

E2

FSH

75-80%

WHO type II

Normogenadotrophic

Normoestrogenic

Normal E2

Normal FSH

10-20%

WHO type III

(Hypergonadotropic

Hypoestrogenic)

E2

FSH

5-10%

WHO type IV

(Hyperprolactinemia)

prolactin

WHO Scientific group, Geneva 1976, Report 514, Rowe et al, 1993 ABOUBAKR ELNASHAR

INVESTIGATIONS 1. Midluteal progesterone

in regular and irregular cycles

{confirm ovulation} In irregular prolonged cycles

Depending upon the timing of menstrual periods, conducted later in the cycle (for example day 28 of a 35-day cycle) and repeated weekly thereafter until the next menstrual cycle starts

2. Basal FSH and LH

Only in

irregular prolonged cycles

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3. Prolactin Only in ovulatory disorder galactorrhoea or pituitary tumour

4. TSH: only if symptoms of thyroid disease

Endometrial biopsy To evaluate the luteal phase: No {no evidence that medical tt of luteal phase defect

improves pregnancy rates]

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5. Ovarian reserve testing

Woman’s age:

An initial predictor of overall chance of success

through natural conception or with IVF

Predictors of ovarian response to Gnt stimulation

High response Low response

16 or more 4 or less Total AFC

3.5 or more

25

0.8 or less

5.5

AMH

ng/ml

pmol/l

Conversion ratio:7

4 or less 8.9 or more FSH IU/L

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Do not use

ovarian volume

ovarian blood flow

inhibin B

E2

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Indications:

≥ 35 ys or

< 35 years of age with risk factors for decreased

ovarian reserve

1. Endometriosis

2. Unexplained infertility

3. Single ovary

4. Previous ovarian surgery

5. Poor response to FSH

6. Previous exposure to chemotherapy or

radiation. (Iii-b)

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Amenorrhea or severe oligomenorrhea

FSH & LH: low

Prolactin: normal

TREATMENT OF ANOVULATION

I. Hypogonadotrophic hypoestrogenic

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1. Reverse the life style factors:

Increase wt if BMI <19 Moderating exercise if high levels of exercise.

Treat stress

2. Gonadotrphins with LH activity or

Pulsatile GnRH (pump)

CC:

not effective

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II. Normogonadotrophic Normoestrogenic

PCOS

2 of 3 (Noterdam definition,2003):

•U/S PCO

•Hyperandrogenism (Clinical or Laboratory)

•Irregular or absent ovulation

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OVULATION INDUCTION IN PCOS NICE, 2013

1. Weigh loss: If BMI >30 K/m2

alone may restore ovulation improve response to ovulation induction agents, positive impact on pregnancy outcomes

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2. One of the following taking into account

•potential adverse effects

•ease and mode of use

•BMI

•monitoring needed:

CC: (not more than 6 m) or

Metformin or

CC + Metformin

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3. CC resistance: one of the following 2nd line tt, depending on •clinical circumstances •woman's preference: CC and met if not already offered as1st line tt or LOD or Gnt US monitoring {measure follicular size and number {reduce the risk of multiple pregnancy and OHSS}

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Weight reduction

Oral anti-estrogens (CC)

Obese &overweight

Normal weight &No weight loss & No ovulation

LOD GnT

No ovulation after 3 cycles. No pregnancy after 6 cycles.

No pregnancy after 6 cycles.

No pregnancy after spontaneous, CC, FSH ovulation

IVF

Other surgical indication Difficult follow up

Less aggressive No desire for surgery

Add metformin IGT &IR

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III. Hypergonadotrophic hypoestrogenic

< 40 yr, 2ndry amenorrhea

Repeated FSH > 20 IU/L

Causes

1. Idiopathic.

2. Genetic.

3. Autoimmune

3. Viral/bacterial infection

4. Pelvic surgery, chemotherapy

5. Galactosemia

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1. Oral contraceptive suppression of gonadotrpins

followed by discontinuation to allow a rebound in

gonadotropins & ovarian function.

2. GnRHa suppression of gonadotropins secretion

followed by high dose gonadotropin injection

3. Glucocorticoids suppression of immune system.

Non of these tts has demonstrated efficacy in RCT

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IV. Hyperprolactinaemia

I. Idiopathic

.Dopamine agonist (anxiety, pregnancy).

Stop during pregnancy

II. Microadenoma

. Dopamine agonist (anxiety, pregnancy).

Stop after 2-3 yr.

. Surgery (rapid growth).

III. Macroadenoma

. Dopamine agonist: long term

. Surgery

(No response, suprasellar extension, pregnancy).

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TYPES OF OVARIAN STIMULATION

Controlled ovarian

stimulation

Super

ovulation

Induction of

ovulation

Anovulatory or ovulatory Anovulatory Patient

Multiple > one One mature

follicle

Objective

IVF IUI

Unexp infert

Anovulatory

Example

Down regulation

Stimulation

Prevent premature

LH surge

Stimulation Stimulation Method

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DRUGS FOR OVARIAN STIMULATION

Anti oestrogens: Clomiphene Citrate, Tamoxifen

Gonadotrophins:

HMG

highly purified ur FSH

Rec. FSH

GnRHa (intranasal-S.C- I.M)

GnRHant (involved in final steps of oocyte maturation)

HCG

Bromocriptine, Metformin, Letrozole

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