Updated: 9/4/2018

Female Infertility

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Snapshot
  • A 35-year-old G1P0 female presents with difficulty becoming pregnant. She and her husband have been trying to conceive for over 12 months, but have been unsuccessful. She reports menarche at age 15 and has had regular periods since then. Her past medical history includes an abortion at age 20 with dilation and curretage procedure. She has also had pelvic inflammatory disorder, treated successfully with antibiotics.
Introduction
  • Inability to conceive
    • after 1 year of unprotected sex in the absence of any known causes of infertility
    • after 6 months if the woman is > 35 years of age or in couples with known risk factors for infertility
  • Epidemiology
    • 10-15% of reproductive-aged couples in the US
    • more common in developing countries
  • Etiologies
    • ovulatory disorder
    • tubal disease
    • uterine or cervical disorders
    • endometriosis
    • idiopathic or advanced maternal age (decreased ovarian reserve) 

Disorders
Category Ovulation
Tubal
Uterine
Pathogenesis
  • Ovaries fail to produce mature oocyte on a regular basis
  • Fallopian tubes fail to capture ovulated ova and/or transport sperm and embryo
  • Uterus fails to allow embryo to implant or support growth/development
Risk factors
  • Increasing age
  • Cytotoxic chemotherapy
  • Radiation therapy
  • Diminished ovarian reserve
  • Smoking
  • Endocrine disorders
    • hypothalamic amenorrhea
  • Pelvic inflammatory disease
    • tubal inflammation
    • especially secondary to salpingitis (Gonorrhea/ Chlamydia)
  • Pelvic tuberculosis
  • Pelvic surgery
  • Complicated abdominal surgery
  • Ectopic pregnancy
  • Uterine leiomyoma
  • Uterine polyps
Etiologies
  • Primary ovarian insufficiency
    • > 35-years-old
  • Endocrine disorders
    • hypothalamic amenorrhea
    • hyperprolactinemia
    • adrenal disease
    • pituitary tumor
  • Polycystic ovarian syndrome 
  • Turner syndrome
  • Asherman's syndrome
    • intrauterine adhesions result from scar formation after uterine surgery
    • after dilation and curettage
  • Uterine growths (leiomyoma, polyps)
  • Congenital uterine anomaly
    • septate uterus
    • unicornate uterus
    • bicornate uterus
    • T-shaped uterus 
Treatment
  • Ovulation induction
  • Oocyte donation
  • Dopamine agonists for hyperprolactinemia
  • Assisted reproductive technology
  • Tubal microsurgery
  • Labaroscopic tubal surgery
  • Assisted reproductive technology
  • Surgery
  • Assisted reproductive technology
 
Presentation
  • Symptoms - etiology dependent and thus patients may report
    • hot flashes
    • chronic pelvic or abdominal pain
    • irregularity of menstrual cycle
    • decreased libido
    • history of chemotherapy or radiation therapy
    • history of endometriosis
    • history of pelvic inflammatory disease
    • psychological distress
    • eating disorder
  • Physical exam - etiology dependent and thus one may find
    • body habitus
      • body mass index > 25 kg/m2 or < 17 kg/m2
        • note, both extremes have been associated with infertility
      • short, stocky, or square-shaped chest may suggest Turner syndrome
    • excessive hair growth
    • acne
    • galactorrhea
    • thyromegaly
    • pelvic exam
      • immobile or mobile uterus
      • discharge from cervix
      • tenderness
Evaluation
  • Diagnosis typically based on history and physical
    • both members of the couple must be evaluated
  • Further testing for female infertility
    • ovulatory function
      • mid-luteal phase serum progesterone level
        • > 3 ng/mL = recent ovulation
        • if < 3 ng/mL, evaluate for causes of anovulation
          • serum prolactin, thyroid-stimulating hormone, and follicle-stimulating hormone (FSH)
          • assess for polycystic ovarian syndrome (PCOS)
        • over the counter urinrary ovulation prediction kit
          • detects leutinizing hormone (LH)
          • 5-10% false positive and false negative rate
            • can detect LH surge, which indicates ovulation
    • ovarian reserve
      • diminished oocyte quality, oocyte quantity, or reproductive potential
      • test ovarian reserve with a day 3 (of menstrual cycle) FSH and estradiol levels
      • other tests
        • clomiphene citrate challenge test
          • provocative test for measurement of FSH
        • anti-Müllerian hormone
          • biochemical marker of ovarian function
          • declines as follicle pool declines
    • fallopian tube patency 
      • hysterosalpingogram (HSG) - first-line
        • tubal occlusion or anatomic abnormality
        • unless laparoscopy is planned
    • uterine cavity
      • saline infusion sonohysterography - preferred unless HSG already being done
        • better for diagnosing intrauterine adhesions, polyps, and congenital anomalies
      • hysterosalpingography
      • hysteroscopy - definitive method to evaluate abnormalities of uterine cavity
        • also offers opportunity for treatment at the time of diagnosis.
Differential Diagnosis
  • Use of contraception
  • Insufficient time to conceive
  • Male infertility
Treatment
  • Depends on the cause of infertility (see chart above)
  • Ovulation induction
    • weight change (either lose or gain weight)
    • clomiphene citrate or other selective estrogen receptor modulator (SERM)
    • metformin
      • for PCOS
    • gonadotropins
    • aromatase inhibitors
  • Oocyte donation
    • for primary ovarian insufficiency
  • Assisted reproductive technology
    • in vitro fertilization
    • intrauterine insemination
  • Surgery to correct anatomic abnormality, obstruction, and endometriosis
Prognosis, Prevention, and Complications
  • Prognosis
    • better chance of fertility with
      • < 32-year-old women
      • presence of ovulatory cycle
      • normal TSH
      • normal levels of anti-müllerian hormone
    • general treatment efficacy
      • 50% pregnancy rate following treatment for infertility
      • best success with ovulatory dysfunction causing infertility
      • less success with severe endometriosis
  • Complications
    • psychiatric complications
      • depression
      • anxiety
      • sexual dysfunction
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.GN.17.4868) A 28-year-old female presents to her gynecologist with one year of secondary infertility. She had one first-trimester spontaneous abortion at age 24, after which she started taking oral contraceptives. That pregnancy was not conceived with her current partner. One year ago, she stopped taking birth control and has been having regular unprotected intercourse with her husband without success. She has regular periods every 28 days with mild dysmenorrhea. The patient has a past medical history of gonorrhea at age 18 which was treated. Her husband has no documented infertility and is a lawyer who cycles on the weekends. She has a family history of coronary artery disease in her father and recurrent pregnancy loss in her mother. At this visit, the patient’s temperature is 98.5°F (36.9°C), pulse is 80/min, blood pressure is 121/82 mmHg, and respirations are 13/min. Cardiopulmonary and abdominal exams are unremarkable. Pelvic exam reveals a normal cervix, retroverted uterus without tenderness, and no adnexal masses. A hysterosalpingogram (HSG) is performed and shown in Figure A. Which of the following is the most likely cause of this patient’s presentation? Review Topic | Tested Concept

QID: 109537
FIGURES:
1

Uterine leiomyomata

0%

(0/61)

2

Tubal blockage

43%

(26/61)

3

In utero exposure to diethylstilbestrol (DES)

30%

(18/61)

4

Uterine retroversion

10%

(6/61)

5

Male factor infertility

16%

(10/61)

L 2 D

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