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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
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
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]
ABOUBAKR ELNASHAR
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 responseLow response
16 or more4 or lessTotal AFC
3.5 or more
25
0.8 or less
5.5
AMH
ng/ml
pmol/l
Conversion ratio:7
4 or less8.9 or moreFSH IU/L
ABOUBAKR ELNASHAR
 Do not use
ovarian volume
ovarian blood flow
inhibin B
E2
ABOUBAKR ELNASHAR
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)
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
Amenorrhea or severe oligomenorrhea
FSH & LH: low
Prolactin: normal
TREATMENT OF ANOVULATION
I. Hypogonadotrophic hypoestrogenic
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
II. Normogonadotrophic Normoestrogenic
PCOS
2 of 3 (Noterdam definition,2003):
•U/S PCO
•Hyperandrogenism (Clinical or Laboratory)
•Irregular or absent ovulation
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
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}
ABOUBAKR ELNASHAR
Weight reduction
Oral anti-estrogens (CC)
Obese &overweight
Normal weight &No weight loss & No ovulation
LODGnT
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
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
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).
ABOUBAKR ELNASHAR
TYPES OF OVARIAN STIMULATION
Controlled ovarian
stimulation
Super
ovulation
Induction of
ovulation
Anovulatory or ovulatoryAnovulatoryPatient
Multiple> oneOne mature
follicle
Objective
IVFIUI
Unexp infert
AnovulatoryExample
Down regulation
Stimulation
Prevent premature
LH surge
StimulationStimulationMethod
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR

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Ovarian Factor Infertility

  • 2. CONTENTS I. EVALUATION TYPES OF ANOVULATION INVESTIGATIONS II. TREATMENT TREATMENT OF ANOVULATION TYPES OF OVARIAN STIMULATION DRUGS FOR OVARIAN STIMULATION ABOUBAKR ELNASHAR
  • 3. 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
  • 4. 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 ABOUBAKR ELNASHAR
  • 5. 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] ABOUBAKR ELNASHAR
  • 6. 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 responseLow response 16 or more4 or lessTotal AFC 3.5 or more 25 0.8 or less 5.5 AMH ng/ml pmol/l Conversion ratio:7 4 or less8.9 or moreFSH IU/L ABOUBAKR ELNASHAR
  • 7.  Do not use ovarian volume ovarian blood flow inhibin B E2 ABOUBAKR ELNASHAR
  • 8. 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) ABOUBAKR ELNASHAR
  • 10. Amenorrhea or severe oligomenorrhea FSH & LH: low Prolactin: normal TREATMENT OF ANOVULATION I. Hypogonadotrophic hypoestrogenic ABOUBAKR ELNASHAR
  • 11. 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 ABOUBAKR ELNASHAR
  • 12. II. Normogonadotrophic Normoestrogenic PCOS 2 of 3 (Noterdam definition,2003): •U/S PCO •Hyperandrogenism (Clinical or Laboratory) •Irregular or absent ovulation ABOUBAKR ELNASHAR
  • 13. 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 ABOUBAKR ELNASHAR
  • 14. 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 ABOUBAKR ELNASHAR
  • 15. 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} ABOUBAKR ELNASHAR
  • 16. Weight reduction Oral anti-estrogens (CC) Obese &overweight Normal weight &No weight loss & No ovulation LODGnT 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 ABOUBAKR ELNASHAR
  • 17. 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 ABOUBAKR ELNASHAR
  • 18. 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 ABOUBAKR ELNASHAR
  • 19. 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). ABOUBAKR ELNASHAR
  • 20. TYPES OF OVARIAN STIMULATION Controlled ovarian stimulation Super ovulation Induction of ovulation Anovulatory or ovulatoryAnovulatoryPatient Multiple> oneOne mature follicle Objective IVFIUI Unexp infert AnovulatoryExample Down regulation Stimulation Prevent premature LH surge StimulationStimulationMethod ABOUBAKR ELNASHAR
  • 21. 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 ABOUBAKR ELNASHAR