Updated: 12/12/2018

Female Infertility

Topic
Review Topic
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Questions
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Evidence
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Snapshot
  • A 27-year-old G0P0 female presents with difficulty with becoming pregnant. She and her husband have been trying to conceive for around 6 months, but have been unsuccessful. On physical exam, she has a short stature with a stocky habitus and broad chest. Labs reveal decreased estrogen, increased LH, and increased FSH.
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
 
 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
Pelvic inflammatory disease
Pelvic tuberculosis
Pelvic surgery
Complicated abdominal surgery
Ectopic pregnancy
Uterine leiomyoma
Uterine polyps
Etiologies Primary ovarian insufficiency
Endocrine disorders
Polycystic ovarian syndrome 
Turner syndrome 
Asherman's syndrome
Uterine growths (leiomyoma, polyps)
Congenital uterine anomaly
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
    • psychological distress
  • Physical exam - etiology dependent
    • depending on etiology, 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
Evalution
  • 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
        • if abnormal, evaluate for causes of anovulation
          • serum prolactin, thyroid-stumlating hormone (TSH), and follicle-stimulating hormone (FSH)
          • assess for polycystic ovarian syndrome (PCOS)
    • 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 decline
    • fallopian tube patency 
      • hysterosalpingogram (HSG) - first-line
        • tubal occlusion or anatomic abnormality
        • contrast spillage into the peritoneal cavity is a normal finding 
    • 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
  • 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
    • metformin
      • for PCOS
  • 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
    • 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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(M1.RP.1) A 32-year-old female presents to your fertility clinic following inability to conceive with her husband for the past two years. The patient reports a long history of oligomenorrhea. Physical examination is notable for acanthosis nigricans around the folds of the neck and hair on the patient's upper lip. Increasing levels of which of the following hormones is likely to help this patient’s fertility problem: Review Topic

QID: 101661
1

Estrogen

17%

(8/47)

2

Leptin

2%

(1/47)

3

Prolactin

9%

(4/47)

4

Follicle stimulating hormone

68%

(32/47)

5

Human chorionic gonadotropin

0%

(0/47)

M1

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