amh screening in infertility

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Role of AMH Screening Dr Sujoy Dasgupta MBBS (Gold Medalist, Hons), MS (OBGY- Gold Medalist), DNB, FIAOG Fellow- Reproductive Endocrinology & Infertility (ACOG, USA) Consultant, Bavishi Pratiksha Fertility Institute, Kolkata Visiting Consultant, RSV Hospital, Kolkata Secretary, Website and Bulletin Committee, Bengal Obstetric and Gynaecological Society (BOGS) 2017-18 Managing Committee Member, BOGS, 2017-18

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Page 1: AMH Screening in Infertility

Role of AMH ScreeningDr Sujoy DasguptaMBBS (Gold Medalist, Hons), MS (OBGY- Gold Medalist), DNB, FIAOG

Fellow- Reproductive Endocrinology & Infertility (ACOG, USA)

Consultant, Bavishi Pratiksha Fertility Institute, Kolkata

Visiting Consultant, RSV Hospital, Kolkata

Secretary, Website and Bulletin Committee, Bengal Obstetric and Gynaecological Society (BOGS) 2017-18

Managing Committee Member, BOGS, 2017-18

Page 2: AMH Screening in Infertility

Anti- Müllerian Hormone (AMH)

• Hormone found in the testes (Sertoli Cells)

• Müllerian regression and sexual differentiation in males

• 1986- Isolated from the Sertoli cells in the testes and the granulosa cells in the ovaries (Picard JY, et al.)

Page 3: AMH Screening in Infertility

Physiology of Follicular Dynamics

Page 4: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

AMH

FSH

70-80 daysLast 20 days

Initial Recruitment Cycle Recruitment Selection Dominance

Paracrine Control

(Gn Independent)

Endocrine Control

(Gn Dependent)

Estrogen

Page 5: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Page 6: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

Page 7: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

Page 8: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

AMH

Page 9: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

AMH

Page 10: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

AMH

FSH

Page 11: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

AMH

FSH

Estrogen

Page 12: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

AMH

FSH

Initial Recruitment Cycle Recruitment Selection Dominance

Paracrine Control

(Gn Independent)

Endocrine Control

(Gn Dependent)

Estrogen

Page 13: AMH Screening in Infertility

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

1st

Migration

• Activin

• Inhibin

• TGF Superfamily

2nd

Migration

• GH

• IGF

• Androgen

AMH

FSH

70-80 daysLast 20 days

Initial Recruitment Cycle Recruitment Selection Dominance

Paracrine Control

(Gn Independent)

Endocrine Control

(Gn Dependent)

Estrogen

Page 14: AMH Screening in Infertility

Role of AMH in Ovarian Dynamics

• Follicular Preservation

• Prevention of unnecessary and excessive recruitment of primordial follicles

• Restriction of follicular sensitivity to FSH

• Indirectly helping mono-follicular development

Page 15: AMH Screening in Infertility

Terminology1. Ovarian Reserve- Number and quality of oocytes present in the

ovary

2. Ovarian Responsiveness- Number of oocytes developed/ retrieved after COH

3. Ovarian Ageing- Decline in quantity and quality of ovarian activity because of individualized rhythm of the “biological clock”

Page 16: AMH Screening in Infertility

Ovarian Reserve

Page 17: AMH Screening in Infertility

When to screen for Ovarian Reserve

• Routine Tests in Sub-fertility (NICE 2013)

1. Semen Analysis

2. Tubal Patency- HSG, HyCoSy, Laparoscopy

3. Mid-luteal serum Progesterone

• Should AMH be included in routine investigation for Infertility?

Page 18: AMH Screening in Infertility

NICE (2013)

For all types of Subfertility-

• Age

Before ART- Any one of

• AMH, FSH, AFC

Page 19: AMH Screening in Infertility

Markers for Ovarian reserve

Page 20: AMH Screening in Infertility

AMH- To screen for Ovarian Reserve

• Superior than other markers

• Paracrine control, independent of HPO endocrine feedback

• Correlates with AFC, FSH, Inhibin B, E2

• Higher sensitivity and specificity than conventional markers

Page 21: AMH Screening in Infertility

• Remains relatively stable throughout the cycle (cf FSH, Inhibin B, E2)

• Low inter-cycle variability

Page 22: AMH Screening in Infertility

Problem with AMH

• Measurement not yet standardized

• Assays- Diagnostic System Lab (DSL), Immuno-Tech Beckman-Coulter (IBC)

• Dispute on lower and higher level

• Poor correlation with oocytequality

Page 23: AMH Screening in Infertility
Page 24: AMH Screening in Infertility

Ovarian Responsiveness

Page 25: AMH Screening in Infertility

AMH to predict Ovarian Responsiveness

• Correlates with number of oocytes retrieved

• Predictive value better than FSH, Inhibin B, E2

• Predictive value equal to AFC

• AMH <1.0 ng/ml- High chance of cycle cancellation

• AMH >4.0 ng/ml- High risk of OHSS

Page 26: AMH Screening in Infertility

• Role in predicting ongoing pregnancy is limited

• Correlates with higher number of D2/3 embryos and better embryo morphology score

• High AMH correlates with higher live birth rate

Aflatoonian A, et al. 2009

Nelson SM, et al. 2009

Fleming R, et al. 2006

Page 27: AMH Screening in Infertility

Ovarian Ageing

Page 28: AMH Screening in Infertility

AMH Screening for Ovarian Ageing

• Earlier marker and more sensitive for POF than FSH

Page 29: AMH Screening in Infertility

When to screen for Ageing

• Family H/O POF

• High Risk of POF

• Cancer Treatment

• Endometriotic Cystectomy

Page 30: AMH Screening in Infertility

AMH in Male

Page 31: AMH Screening in Infertility

AMH Screening in Male

• Secreted from Sertoli Cells

• Under control of gonadotrophins, suppressed by testosterone

• Serum AMH remains high until onset of puberty

• Value remains low in adult male

• Important in childhood to screen for hypogonadism

• Low AMH at puberty → Precocious puberty

• High AMH at puberty → Delayed puberty

Page 32: AMH Screening in Infertility

Possible Role in Azoospermia

• AMH- OA < NOA

• Marker (Noninvasive) of successful sperm retrieval in OA

• Normal AMH in Sertoli-cell-only Syndrome

Page 33: AMH Screening in Infertility

Number or Value

Page 34: AMH Screening in Infertility

Low AMH = Poor Ovarian reserve???

Ovum Donation IVF DHEA Clinical Correlation

Page 35: AMH Screening in Infertility

Conclusion

• Good predictor of ovarian reserve

• Predicts ovarian response to Gn Stimulation

• Predicts the probability of cycle cancellation and hyper-response in ART

• Levels are higher in PCOS

• Could be a potential marker of obstructive azoospermia

• Role as isolated marker- ?

Page 36: AMH Screening in Infertility