Female Infertility

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

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