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

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.)

Physiology of Follicular Dynamics

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

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Primordial Follicle

Small Preantral

Large Preantral

Small Antral (2-7 mm)

Large Antral(8-12 mm)

Preovulatory

Atresia Atresia Atresia

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

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

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

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

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

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

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

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

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”

Ovarian Reserve

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?

NICE (2013)

For all types of Subfertility-

• Age

Before ART- Any one of

• AMH, FSH, AFC

Markers for Ovarian reserve

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

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

• Low inter-cycle variability

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

Ovarian Responsiveness

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

• 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

Ovarian Ageing

AMH Screening for Ovarian Ageing

• Earlier marker and more sensitive for POF than FSH

When to screen for Ageing

• Family H/O POF

• High Risk of POF

• Cancer Treatment

• Endometriotic Cystectomy

AMH in Male

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

Possible Role in Azoospermia

• AMH- OA < NOA

• Marker (Noninvasive) of successful sperm retrieval in OA

• Normal AMH in Sertoli-cell-only Syndrome

Number or Value

Low AMH = Poor Ovarian reserve???

Ovum Donation IVF DHEA Clinical Correlation

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- ?