Investigations to evaluate Infertility Dr Atin Singhai Assistant Professor Department of Pathology KGMU, Lucknow

Background Definition: 10-15% couples affected Etiology 1 yr unprotected coitus without conception 10-15% couples affected Etiology Couples: 35% Tubal and pelvic pathology 35 % Male problems 15% Ovulatory dysfunction 10% Unexplained 5% unusual causes

Background Etiology Normal couple: Fertility decreases with age Women: 40% Tubal and pelvic pathology 40% Ovulatory dysfunction 10% Unexplained Infertility 10% Unusual causes Normal couple: 25-30% chance of pregnancy per ovulatory cycle Fertility decreases with age

Infertility Time of Exposure % Pregnant 3 months 60% 6 months 70% 1 year 85% 18 months 90%

Approach to Infertility DDX Tests/Inv Dx Rx

Approach to Infertility Production Storage Delivery

Male Infertility 1. Production: Hypothalamus Anterior Pituitary Testes

Hypothalamic-Pituitary-Gonadal Axis

Male Infertility 1. Production Hypothalamus Congenital abnormalities of hypothalamus e.g. Kallman’s syndrome Starvation, stress or severe illness Tumors (craniopharyngioma, metastatic tumor) Head injury Inflammation (sarcoidosis) Infection (tuberculosis) Drugs: marijuana

Male Infertility 1. Production: Pituitary Endocrine: thyroid, prolactin Tumors Inflammation: sarcoidosis, meningitis Infiltration Infarction Trauma/XRT Drugs: anabolic steroids

Male Infertility Production: Testes: Congenital: Klinefelters (XYY), developmental disorders Disorders of gonadal steroidgenesis Infection: chlamydia, prostatitis, mumps orchitis Autoimmune Cryptorchidism Tumors; chemo/XRT Drugs / alcohol Vascular: testicular torsion

Male Infertility 2. Storage: Temperature Rise in scrotal temperature Occupation Varicocoele

Male Infertility 3. Delivery: Impotence/Ejaculation Neurogenic: medications (α-blockers, methyldopa) Endocrine: diabetes Congenital: absence vas deferens (CF) Genetic: cystic fibrosis Primary ciliary dyskinesia: Kartagener syndrome Hypospadia Vasectomy

Male Infertility History: Previous children Infections: prostatitis, STD, mumps orchitis Trauma to head or testicles Surgery to testicles or hernia Occupation (sitting, bio hazards) Chemo or Radio therapy Ethanol or Smoking Medication Medical history (DM, HTN) Previous investigations

Male Infertility Physical Anatomy (meatus) Testicular size Varicocele (valsalva) Rectal exam (protatitis, discharge)

Male Infertility Investigations: semen analysis If abnormal: Abstain 2-4 days prior At least 2 samples over different period of time If abnormal: Blood work: FSH, LH, TSH, testosterone, PRL Testicular U/S Chromosomal analysis

Male Infertility Semen analysis: WHO (1992) Volume > 2.0 mL Sperm > 20 million/mL Motility > 50% forward progression or > 25% rapid progression within 60 min Morphology > 30% normal forms WBC < 1 million/mL

Male Infertility Tx / Interventions: Treat underlying causes Intrauterine Insemination (IUI) Intracytoplasmic Sperm Injection (ICSI)

Female Infertility Fecundability: probability of achieving a pregnancy within 1 menstrual cycle (25%) Fecundity: ability to achieve a live birth within 1 menstrual cycle (6%)

Female Infertility Production Storage Delivery

Female Fertility Production: Hypothalamus Pituitary Ovary

Hypothalamic-Pituitary-Gonadal Axis

Female Infertility Hypothalamus: Stress Exercise Eating disorders Psychogenic Congenital/genetic: Kallman’s syndrome (hyposmia & hypoplasia olfactory lobes of brain) Starvation/stress or severe illness Tumors (craniopharyngioma, metastatic tumor) Head injury Inflammation (sarcoidosis) Infection (tuberculosis) XRT Drugs

Female Infertility Pituitary: Sheehan syndrome Tumors: Pituitary adenoma, metastatic Empty sella syndrome Inappropriate gonadal steroid feedback: estrogen excess: obesity/ tumors estrogen deficiency: aromatase deficiency/ ER gene mutation androgen excess: adrenal or ovarian PCOS Testicular feminization (46 XY) - absence androgen receptors

Female Infertility Ovary Gonadal dysgenesis - Turner’s Syndrome 45XO or mosaics 46 XX/45 XO Testicular feminization XRT / Chemo for childhood malignancies Premature ovarian failure

Female Infertility Storage (R.P.L. unless severe) Uterine abnormalities Mullerian Agenesis: Mayer-Rokitansky-Kuster- Hauser syndrome Leiomyoma Luteal phase deficiency

Female Infertility Delivery: Uterine abnormalities Vaginal septum Tubal Disease Infections/ STD/PID Ruptured appendix Septic abortion Endometriosis

Female Infertility History: Age GTPAL Regulatory of period Prolactin S/S Thyroid S/S Infections, Surgeries Medication, Smoking, Ethanol Medical history Previous investigations

Female Infertility Examination: Thyroid Breast (milk) Abdomen (masses, scars) Vaginal (abnormalities) Bimanual (Uterus, masses)

Investigations Blood work: Imaging: Diagnostic TSH PRL D3 FSH D3 LH Luteal phase Progesterone Imaging: Pelvic Ultrasound HSG Diagnostic Laparoscopy (later)

Treatment Treat the underlying cause Medical Surgical

Treatment Anovulation: IVF ICSI Clomiphene induction  IUI Gonadotropin  IUI IVF Bilateral tubal disease Unexplained infertility after Gonadotropin + IUI failure. Failure of the above ICSI Male factor Unexplained infertility

Take Home Points DDx – Hx – Px – Inv - Rx Age is important factor for female Hypothalamic-Pituitary-Gonadal axis central in working up both male and female infertility Investigations: Male: Sperms Female: Tubes (HSG) + Ovaries (FSH, LH, PRL, TSH)

Multiple Choice Questions

Infertility is defined as unprotected coitus for ___ months, without conception : 3 6 9 12

Spermatogenesis and sperm maturation is regulated by : Leydig Cells Sertoli Cells Vas Deferens Intermediate Cells

Cause/s of male infertility is / are : Kallaman’s syndrome Craniopharyngioma Marijuana abuse All of the above

Normal semen count is ___ million / ml ≥ 15 ≥ 20 ≥ 25 ≥ 30

Indication/s for semen analysis is / are : Investigation for infertility to check effectiveness of vasectomy for selection of donor for artificial insemination All of the above

Thank you