How to proceed with a 25-year-old woman presenting with primary infertility, a uterus to cervix ratio of 1:1, and a severely diminished ovarian reserve indicated by an Anti-Mullerian Hormone (AMH) level of 0.65?

Management of Primary Infertility with Uterine Hypoplasia and Severely Diminished Ovarian Reserve

This 25-year-old woman requires urgent evaluation for premature ovarian insufficiency (POI) and congenital uterine anomaly, with immediate referral to reproductive endocrinology for fertility preservation counseling and assisted reproductive technology (ART) planning. The combination of a 1:1 uterus-to-cervix ratio (indicating uterine hypoplasia) and AMH of 0.65 ng/ml (severely diminished ovarian reserve) represents dual reproductive challenges requiring specialized intervention.

Immediate Diagnostic Workup

Confirm Premature Ovarian Insufficiency

• Measure FSH and estradiol levels to confirm POI, as these are the recommended primary tests when AMH suggests diminished ovarian reserve 1, 2
• FSH and estradiol should be obtained while not on hormonal contraception, as these can artificially suppress values 1
• At age 25 with AMH 0.65 ng/ml (below the 0.7 ng/ml threshold), this patient faces significantly increased miscarriage risk (OR 1.91; 95% CI 1.40-2.60) if pregnancy is achieved 1, 2

Evaluate Uterine Anatomy

• The 1:1 uterus-to-cervix ratio indicates uterine hypoplasia, which may represent Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or other Müllerian anomalies
• Obtain pelvic MRI to fully characterize uterine anatomy, endometrial cavity dimensions, and assess for associated renal anomalies
• Evaluate whether functional endometrium is present and adequate for embryo implantation

Critical Fertility Counseling Points

Ovarian Reserve Implications

• AMH 0.65 ng/ml indicates severely diminished ovarian reserve with substantially reduced fertility potential 2, 3
• This level suggests a dramatically shortened reproductive window, requiring urgent action if biological parenthood is desired 2
• Women with AMH <0.7 ng/ml have 91% increased odds of miscarriage compared to those with normal AMH 1, 2
• The absolute miscarriage risk increases by approximately 7% (from baseline 20% to 27% at her age) 1

Uterine Factor Considerations

• Uterine hypoplasia may preclude pregnancy carrying capacity depending on severity
• If the uterine cavity is inadequate, gestational surrogacy may be the only viable option for biological parenthood

Recommended Management Algorithm

Step 1: Urgent Reproductive Endocrinology Referral

• Refer immediately to reproductive endocrinology/gynecology for comprehensive fertility assessment 1, 2
• Time is critical given the severely diminished ovarian reserve at age 25

Step 2: Fertility Preservation Discussion

• Discuss oocyte or embryo cryopreservation urgently before further ovarian reserve decline 2
• Even with low AMH, some oocytes may be retrievable, though response to ovarian stimulation will likely be poor 4
• AMH predicts quantity of oocytes but not quality; age 25 is favorable for oocyte quality despite low quantity 4, 5

Step 3: ART Planning Based on Uterine Capacity

• If uterine cavity is adequate (>4 cm length with functional endometrium): Proceed with IVF/ICSI with own oocytes and autologous pregnancy attempt
• If uterine cavity is inadequate: Counsel regarding gestational surrogacy using own oocytes (if retrievable) or donor oocytes
• If no oocytes retrievable: Discuss donor oocyte options with or without gestational carrier depending on uterine capacity

Step 4: Antral Follicle Count Assessment

• Obtain transvaginal ultrasound with antral follicle count (AFC) to complement AMH assessment 3, 6
• AFC strongly correlates with AMH (r=0.972) and provides additional prognostic information for ART response 6, 7
• AFC is the most established method for ovarian reserve assessment despite operator dependence 3

Important Clinical Caveats

AMH Interpretation at Age 25

• AMH is most reliable in women ≥25 years where validated normative data exist 3
• At age 25, this patient's AMH 0.65 ng/ml is definitively abnormal and not attributable to normal fluctuation 2, 3

Miscarriage Risk Counseling

• The increased miscarriage risk (OR 1.91) is independent of age in women with severely low AMH 1
• This represents a 35% relative increase in miscarriage rate, though absolute risk increase is modest (7%) 1
• The mechanism may involve increased aneuploidy rates in oocytes from diminished ovarian reserve 1, 2

Assay Variability

• Different AMH assays yield varying results; interpret in context of specific laboratory reference ranges 2, 3
• The lack of international AMH standardization limits direct comparison between studies 1, 3

Contraindications to Delay

• Do not delay fertility treatment based on low AMH alone; this should guide dosing and expectations, not withhold treatment 4
• The American Society for Reproductive Medicine recommends women with diminished ovarian reserve pursue fertility evaluation and treatment promptly 2

Prognosis and Expectations

• Pregnancy is possible but likelihood is significantly reduced with AMH 0.65 ng/ml 2
• Success depends critically on uterine anatomy adequacy and response to ovarian stimulation
• Age 25 is favorable for oocyte quality despite poor quantity, providing some advantage over older women with similar AMH 4
• If uterine anatomy precludes pregnancy, gestational surrogacy offers good success rates with young oocytes (if retrievable)