Infertility

Question 1

Infertility

Answer 1

• A woman who is unable to achieve pregnancy after 12 months or more of unprotected intercourse or inseminations.

Question 2

primary infertility

Answer 2

• “When a woman is unable to ever bear a child, either due to the inability to become pregnant or the inability to carry a pregnancy to a live birth she would be classified as having primary infertility. Thus women whose pregnancy spontaneously miscarries, or whose pregnancy results in a still born child, without ever having had a live birth would present with primarily infertility.”- WHO

Question 3

secondary infertility

Answer 3

• “When a woman is unable to bear a child, either due to the inability to become pregnant or the inability to carry a pregnancy to a live birth following either a previous pregnancy or a previous ability to carry a pregnancy to a live birth, she would be classified as having secondary infertility. Thus those who repeatedly spontaneously miscarry or whose pregnancy results in a stillbirth, or following a previous pregnancy or a previous ability to do so, are then not unable to carry a pregnancy to a live birth would present with secondarily infertile.” -WHO

Question 4

infertility: female factors, male factors, social factors, environmental factors

Answer 4

• Female Factors
  
  • Ovulatory status?
  • Tubes open (endometriosis? Hx of PID?)
  • Scar tissue?
  • Egg quality?
  • Uterine anatomy?
• Male Factor
  
  • Count, Motility, Morphology?
  • Sexual dysfunction?
  • Medications?
  • Developmental? (XXY, cryptorchidism?)
• Social Factors
  
  • Timing of intercourse or ovulation?
  • Use of lubricants?
  • Smoking, drugs?
• Environmental Factors
  
  • BPA?
  • Mercury?
  • Chemical Exposure?
• It is the most common birth defect of the male genitalia.^<a>[1]</a> In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis. However, about 80% of cryptorchid testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall. Cryptorchidism is distinct from monorchism, the condition of having only one testicle. Reduced spermatogenesis in cryptorchid testes is due to temperature differences. high rate of anomalies of the epididymis

Question 5

sperm maturation

Answer 5

• Sperm maturation starts out in the seminiferous tubules in the testes and then completes in the epididymis. Takes around 120 days.
• A sperm cell consists of:
  
  • Head: contains the chromosomes and is surrounded by an acrosome (contains the enzymes required to penetrate the egg)
  • Mid piece: contains the mitochondria which supplies the energy to reach the egg
  • Tail: propels the sperm
• If any portion of the above is compromised, it can lead to infertility.

Question 6

infertility workup/diagnosis

Answer 6

• Female Blood and Diagnostic Tests:
• FSH (Follicle Stimulating Hormone) and Estradiol (CD 2 or 3)
• AMH (Anti-Mullerian Hormone), Prolactin, RPL Panel
• TSH (Thyroid Stimulating Hormone)
• Prenatal Labs/CBC/Vit D/Prolactin
• Fasting Blood Sugar/Free and Total Testosterone
• Chromosome Analysis/Genetic Screening
• Ultrasound
• SIS (Saline Infusion Sonogram) or HSG (Hysterosalpingogram)
• Male Blood and Diagnostic Tests:
  
  • FSH and Estradiol
  • TSH
  • Semen Analysis
  • Chromosome Analysis
• AMH: in male fetus, activated by Sertoli cells-> inhibit dev of female repro tract=mullerian ducts. In females, produced in granulosa cells, regulating folliculogenesis in selection of single dominant follicle.

Question 7

infertility: female factor

Answer 7

• PCOS: High testosterone to estrogen ratio = random or anovulatory cycles. Increased FBG and fasting insulin.
• Hypothalamic Amenorrhea (HA): Hypothalamus does not produce GnRH = anovulatory cycles.
• Egg Quality/Decreased Ovarian Reserve (DOR): High FSH/Estradiol, low AMH levels
• Factors affecting ovulation: Elevated Prolactin, Thyroid, Stress, Fatigue….

Question 8

uterine anomalies

Answer 8

• Fibroids: Subserosal vs Intramural vs Submucosal
• Uterine Septum/Bicorneate vs Didelphus

Question 9

pelvic and fallopian tube adhesions

Answer 9

• Old Chlamydia infection
  
  • most common cause
  • “Silent infection”
  • cultures negative
• Surgery unhelpful in most cases
• Surgery
  
  • success in youngest (<34) patients
  • 50% of success within 2 years
  • next 50% within 11 years
• Adhesions reform!!!
• Endometriosis NEVER goes away
• Repeat surgery even less helpful
• Bottom line: IVF best option
• Chlamydia is known as a ‘silent’ infection because most infected people are asymptomatic and lack abnormal physical examination findings. It’s estimated that only about 10% of men and 5-30% of women with laboratory-confirmed chlamydial infection develop symptoms.

Question 10

infertility: male factor

Answer 10

• Normal semen:
  
  • 2 cc volume
  • 40 million/cc count
  • 40% active motility
  • 60% normal shapes/morphology
• Mild male factor:
  
  • 5 -20 million total motile “good-looking” sperm
• Severe male factor:
  
  • < 5 million total motile “good-looking” sperm
• “Good looking” sperm = Volume x Count x Active x Normal shapes
• Goal ≥ 20 “good-looking” million in sample
• Correct remediable causes:
  
  • Scrotal Heat – illness, hot tubs, laptop, cellphone
  • Cycling - bike or motorcycles
  • Change medications - gout, antihypertensives, H₂ blockers (Cimetidine, Ranitidine)
  • Excessive alcohol, Marijuana
  • Takes 3 month minimum to see changes
• Send to urologist:
  
  • Examination (undescended testes, varicocele)
  • Hx of Vasectomy?
  • Poor semen analysis result
• Patient who tried to conceive >12 months then hubby told her he had a vasectomy after kids in his previous marriage. Marijuana can lower sperm count, motility and ability to penetrate the egg. and reduce sexual performance and testosterone

Question 11

oligospermia

Answer 11

• This patient had + PMHx: mumps @ 7yo. Referred to urologist for further evaluation and management.
• Screen for testosterone use, chromosome analysis for deletions in Y, hormone panel.

Question 12

infertility: treatments

Answer 12

• PCOS
  
  • treat insulin resistance and elevated glucose (metformin)
  • ovulation induction (Clomid, Femara, Fertility Injections)
  • weight loss
  • +/- IUI (Intrauterine Insemination)
  • +/- IVF (In-vitro Fertilization) if sperm issues
• HA
  
  • ovulation induction (Clomid, Femara, Fertility Injections)
• DOR
  
  • IVF
  • Donor Egg
• Uterine Issues
  
  • IVF + Gestational Carrier
• Other Endocrine Issues
  
  • Hyperprolactinemia: Rx Bromocriptine
  • Thyroid: Tx underlying issue (REIs like TSH between 1-2)
• Sperm Issues
  
  • IVF + ICSI (Intracytoplasmic Sperm Injection) vs PICSI
    
    • (Physiological Intracystoplasmic Sperm Injection)
  • Donor Sperm

Question 13

diet and lifestyle modification

Answer 13

• Stop
  
  • Tobacco, ETOH, recreational drugs
  • Exercise (if d/t HA)
• Start
  
  • Eating healthy
  • Sperm friendly foods (Spinach, liver, broccoli, almonds, citrus fruits, beef, lamb, pumpkin seeds, sesame seeds,
  • yogurt, shrimp, and other iron and zinc rich foods.)
  • Exercise, decrease BMI (if warranted)
  • Vitamins (Folic Acid, DHEA, Fish Oil, CoQ10)

Question 14

acupuncture

Answer 14

• Enhanced GnRH secretion from the hypothalamus
• Cardiovascular system
  
  • Slows heart rate
  • Lowers blood pressure
• Neurological
  
  • Reduces pain
  • increases b endorphinlevels
• Uterus
  
  • Improves endometrial thickness
  • Improves uterine artery blood flow
• Improves pregnancy rates
• Results in higher implantation rates

Question 15

infertility extras

Answer 15

• Egg quality @:
  
  • 30 YO = 50% chromosomally abnormal
  • 35 YO = 75% chromosomally abnormal
  • 40 YO = 90% chromosomally abnormal
  • 42 YO = 98% chromosomally abnormal
• NIPT (Non-Invasive Pre-ntatal Testing)
  
  • Complete genome screening of fetus via mom’s blood @ 9wks GA +
    
    • 22q deletion syndrome (DiGeorge)
    • 5p (Cri-du-chat syndrome)
    • 15q (Prader-Willi/Angelman syndromes)
    • 1p36 deletion syndrome
    • 4p (Wolf-Hirschhorn syndrome)
    • 8q (Langer-Giedion syndrome)
    • 11q (Jacobsen syndrome)
• PGT-A: Pre-Implantation Genetic Testing for Aneuploidy & Mitoscore

PGT-A screening of embryos for chromosomal abnormalities vs PGT-M (monogenic/single gene defects) prior to transferring embryo/s.

Question 16

day 5 embryo trophectoderm biopsy for PTG-A

Answer 16

• The trophectoderm cells will eventually become part of the placenta and other embryonic structures. They do not become part of the fetus.

Question 17

Fertilome, egg freezing or embryo banking, using a gestational carrier

Answer 17

• Fertilome
  
  • Multigene test for genetic factors that may predispose to female infertility (ie. DOR, RPL, endometriosis)
• Egg Freezing or Embryo Banking
  
  • Fertility Preservation
  • Underlying Medical Conditions (eg. Cancer)
• Using a Gestational Carrier
  
  • RPL (Recurrent Pregnancy Loss)
  • Hx of pregnancy complications
  • Uterine anomalies

Question 18

when to refer your patients to an REI

Answer 18

• 3 months of unprotected intercourse. Why wait the 6 months – 1 year?!
• Family history of recurrent pregnancy loss, infertility, early menopause in mother of female patient, genetic disorders…
• Endometriosis!!!!! “How can pregnancy be the cure if they can’t get pregnant?”
• Fertility preservation: freeze eggs, sperm and/or embryos!
• When it doubt, refer it out!