InfertilityUNC School of Medicine

Obstetrics and Gynecology ClerkshipCase Based Seminar Series

Objectives for Infertility Define infertility

Describe the causes of male and female infertility

Describe the evaluation and initial management of an infertile couple

List the psychosocial issues associated with infertility

Failure of a couple to conceive after 1 year of regular intercourse without use of contraception Primary infertility – No prior pregnancies Secondary infertility – Prior pregnancy

Definition

Infertility affects 10-15% of reproductive-age couples in the U.S.

Approx. 85% of couples achieve pregnancy within 1 year Conception rate (fecundability)

25% conceive within 1 mo. 60% conceive within 6 mo.’s 75% conceive within 9 mo.’s 90% conceive within 18 mo.’s

Prevalence

Successful conception requires a specific series of events:1. Ovulation of competent oocyte2. Production of competent sperm3. Juxtaposition of sperm and oocyte in a patent reproductive tract4. Fertilization5. Generation of a viable embryo6. Transport of the embryo to the uterine cavity7. Implantation of the embryo into the endometrium

Etiology

Major causes of of infertility: Female factor – 60%

Ovulatory dysfunction Abnormalities of female reproductive tract Peritoneal factors Reproductive aging

Male factor – 20% Abnormal semen quality Abnormalities of male reproductive tract

Idiopathic – 15%

Infertility in ~ 20-40% of couples has multiple causes

Etiology

Female Duration of infertility and prior evaluation or therapy Menstrual cycle (length and characteristics)

Symptoms associated with ovulation (e.g. breast tenderness, bloating, mood changes)

Full OBHx and GynHx Prior pregnancies, surgeries, or STD’s

Sexual history (frequency of intercourse) Chronic medical illness Family history (infertility, birth defects, genetic disorders) Social history (smoking, EtOH, drugs)

Infertility: History

Male Prior children Genital tract infections Genital surgery or trauma Chronic medical illness Medications (e.g. Furantoins, CCB) EtOH, drugs, or smoking Sexual history (frequency of intercourse)

Infertility: History

Female Height, weight , BMI Pelvic exam

Masses Tenderness (Adnexa, Cul-de-sac) Structural abnormalities (Vagina, Cervix, or Uterus)

Male (Urologist referral) Evidence of androgen deficiency Structural defects (e.g. varicocele, hernia)

Infertility: Physical Exam

Male factor: Evaluation

Initial evaluation Further evaluationMale Factor Semen analysis

Urologic evaluationFSH, LH, and testosterone levelGenetic evaluationEpididymal sperm aspiration (PESA, MESA)Testicular biopsy

Element Reference value

Ejaculate volume 1.5-5.0 mL

pH > 7.2

Sperm concentration > 20 million/mL

Motility > 50%

Morphology > 30% normal forms

Male factor: Evaluation

Semen analysis Following 2-4 day period of abstinence Repeated x1 for accuracy

Male factor: Evaluation

Urologic evaluation Physical Exam

Varicocele Congenital absence of vas deferens (CAVD)

Transrectal ultrasound Vasography, Seminal vesiculography Epididymal sperm aspiration (PESA or MESA)

Male factor: Evaluation

Endocrine evaluation Indication: Oligospermia (< 10million/mL) or sexual dysfunction (decreased

libido, impotence) FSH, LH, testosterone

Genetic evaluation Indication: Azoospermia (no sperm) CFTR mutation Karyotype (Klinefelter’s, Y chromosome deletion)

Testicular biopsy Indication: Nonobstructive azoospermia

Palpable vasa Normal testis volume Normal FSH/LH

Female factor: Evaluation

Factor Initial evaluation Further evaluationOvulation History and physical exam

Basal body temp chartingOvulation predictor kit

Mid-luteal phase progesterone levelEndocrine testingEndometrial biopsy

Reproductive tract (uterus or fallopian tubes)

Hysterosalpingogram (HSG)Ultrasound

Saline-infusion sonographyHysteroscopyLaparoscopy

Peritoneal LaparoscopyReproductive aging FSH, estradiol, or AMH

Female factor: Menstrual Cycle

Ovulation Initial evaluation:

Basal body temp – rise for > 10 days indicates ovulation Ovulation predictor kit – detects LH surge in urine

Further evaluation: Mid-luteal phase progesterone level - level > 3 ng/mL provides

qualitative evidence of recent ovulation Endocrine testing (TSH, prolactin, FSH, LH, Estradiol, DHEA-S) Endometrial biopsy

Not routinely performed

Female factor: Evaluation

Reproductive tract Initial evaluation:

Hysterosalpingogram (HSG) Detect uterine anomalies (septate or bicornuate uterus, uterine

adhesions, uterine leiomyoma) Detect patency of fallopian tubes (occlusion, hydrosalpinx, salpingitis)

Ultrasound – alternative to HSG to evaluate uterus

Female factor: Evaluation

Reproductive tract Further evaluation:

Saline-infusion sonography (SIS) Hysteroscopy Laparoscopic chromotubation

Female factor: Evaluation

Peritoneal factors Laparoscopy

Endometriosis Pelvic/adnexal adhesions

Female factor: Evaluation

Reproductive aging Indications:

> 35 years of age 1st degree relative with early menopause Previous ovarian insult (surgery, chemotherapy, radiation) Smoking Poor response to ovarian stimulation Unexplained infertility Candidate for IVF

Female factor: Evaluation

Reproductive aging Cycle day 3 serum FSH and estradiol

Abnormal (“diminished ovarian reserve”) FSH > 10 IU/L Estradiol > 75-80 pg/mL

Clomiphene citrate challenge test Cycle day 10 serum FSH

Serum antimullerian hormone (AMH)

Female factor: Evaluation

Prevalence ~ 15% Factors that cannot be identified

Sperm transport defects Inability of sperm to fertilize egg Implantation defects

Idiopathic Infertility

Infertility: Management

Male Factor Avoidance of alcohol Scheduled intercourse Ligation of venous plexus for significant varicocele Intrauterine insemination (IUI) with washed sperm Intracytoplasmic sperm injection (ICSI) + IVF Donor sperm insemination

Anovulation Oral medications:

Clomiphene citrate Dopamine agonists (Bromocriptine) - hyperprolactinemia

Injectable medications: Gonadotropins (FSH/hMG, hCG)

Laparoscopic “ovarian drilling” Complications: Ovarian hyperstimulation, Multiple pregnancy

Infertility: Management

Reproductive tract abnormality Uterine: Myomectomy, Septoplasty, Adhesiolysis Tubal: Microsurgical tuboplasty, Neosalpigostomy Peritoneal: Laparascopic treatment of endometriosis, Adhesiolysis

Idiopathic infertility Ovarian stimulation + IUI

Clomiphene or gonadotropins (hMG, hCG) IVF

Infertility: Management

Used for: Severe male factor Tubal disease Couples who failed other treatments

Requires Controlled ovarian hyperstimulation Retrieval of oocytes In vitro fertilization and embryo transfer

Procedures IVF + embryo transfer (IVF-ET) Intracytoplasmic sperm injection + embryo transfer (ICSI-ET) Donor egg IVF + embryo transfer

Infertility: Management (IVF)

The psychological stress associated with infertility must be recognized and patients should be counseled appropriately.

Psychological

Bottom Line Concepts Infertility is defined as one year of unprotected coitus without

conception. Infertility may be primary or secondary. Multiple causes must be considered for infertility diagnosis and

treatment. Male and female reproductive tract anatomy and physiology should be

reviewed in order to generate a full differential diagnosis. Components of an initial infertility workup include a thorough history

and physical examination. Laboratory investigations include a semen analysis, documentation of ovulation, and hysterosalpingogram.

Dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis and medical illness, including thyroid disease and pituitary tumors, can cause ovulatory disturbances.

Success rates with IVF depend on the etiology of infertility and the age of the female partner.

References and Resources

APGO Medical Student Educational Objectives, 9th edition, (2009), Educational Topic 48 (p102-103).

Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 38 (p337-346).

Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 34 (p371-378).