Infertility Flashcards
Infertility
The inability to achieve pregnancy after 12 months of unprotected intercourse
• Infertility affects about 12% percent of the reproductive-age population
Female Factors causing infertility
40-50% of cases • Ovulatory dysfunction • Tubal factor • Endometriosis • Advanved maternal age • Polycyctic ovary syndrome (PCOS) • Luteal phase defect • Toxic insult (radiation, chemo) • Uterine abnormality • Genetic disorder (e.g., Turner syndrome) • Infection
Male Factors causing infertility
30-40% of cases • Testicular injury • Primary testicular failure • Varicocele (varicose vein that alters testicular temperature and sperm production) • Infection • Impotence • Spinal cord injury
Combined and Idiopathic factors causing infertility
Combined factors: 30% of cases
• Both partners have factors contributing to infertility
Idiopathic: 20% of cases
• Unexplained infertility
Day 3 Labs
• FSH measured on Day 3 of menstrual cycle
(LMP 3/9/14; Date collected 3/11/14)
Normal Adult Female Values:
Follicular: 2.5 – 10.2 mIU/mL
Midcycle: 3.4 – 33.4 mIU/mL
Luteal: 1.5 – 9.1 mIU/mL
Pregnant: 10 mIU/mL indicates poor prognosis
Hysterosalpingogram (HSG)
X-ray with contrast dye to determine whether tubes are open or blocked
Semen Analysis
Parameter Normal Range Volume > 2.0 mL Liquefaction < 60 minutes Viscosity Moderate to Low Concentration > 20 * 106 /mL Motility > 50% WHO Morphology > 15%
Treatment of Infertility
Most infertility cases (85% to 90%) are treated with conventional medial therapies such as dietary modification, exercise, medication, or surgery
• E.g., progesterone to treat luteal phase defect
• E.g., metformin and exercise for PCOS
• E.g., Fertility drugs for ovulation induction with intrauterine insemination (IUI)
• E.g., Surgical removal of uterine polyp (non-cancerous growth attached to endometrium extending into uterine cavity) or septum (wedge-like partition within uterine cavity)
In vitro fertilization (IVF) and related treatments account for less than 3% of infertility services
Intrauterine Insemination (IUI) Steps
- May involve controlled ovarian stimulation
- Transvaginal ultrasound
- Trigger ovulation at the appropriate time
- Intrauterine insemination
May involve controlled ovarian stimulationPart 1: Clomiphene Citrate
• Increase body’s FSH&LH secretion during early to mid-follicular phase
• Stimulate follicle growth
• Permit more than one follicle to mature
a. Clomiphene citrate (Clomid)- Estrogen antagonist (a SERM)
• Blocks negative feedback by estradiol and thus stimulates FSH&LH secretion
• May change quality of cervical mucus and reduce endometrial proliferation
May involve controlled ovarian stimulation
Part 2: Letrozole
b. Letrozole (Femara)- Aromatase inhibitor
• Prevents ovarian and peripheral conversion of androgens to estrogens
• Lower estradiol permits more FSH&LH secretion
May involve controlled ovarian stimulation
Part 2: FSH
c. FSH
• Directly stimulates follicle development
• Low doses stimulate growth of 2-3 follicles
• Some brands are purified from urine of post-menopausal women (hMG)
• Other brands are recombinant hFSH
Transvaginal ultrasound
- Determine number and size of lead follicles
- Cancel cycle if there are too many follicles (to avoid multiple gestation)
Ideal Conditions for LH surge:
• Lead follicle will be about 15-18mm
• Endometrium will be about 6-10 mm think
• Developing follicles are down from cohort targeted for that month (# in cohort declines with age)
**Goal is 2-3 good follicles
Trigger ovulation at the appropriate time
Mimic LH surge to stimulate ovulation
• Human chorionic gonadotropins (hCG)
o Some brands are purified from urine of pregnant women
o Other brands are recombinant hCG
• Ovulation occurs approximately 36 h after hCG injection
. Intrauterine insemination
• Washed sperm are placed in uterus by catheter just prior to expected time of ovulation
(“Turkey baster” method)
**Washing sperms removes prostaglandins
IUI cycle summary
Days 1- 13: Follicular Phase • Days 3-7: Clomid • Day 10: Ultrasound • Day 12: hCG trigger Day 14: Ovulation and IUI Days 15-28: Luteal Phase • Day 28: Pregnancy test
Assisted Reproductive Technology (ART)
Any procedure where both sperm and oocytes are handled outside of body
• Although various definitions have been used for ART, this definition is used by CDC
Does NOT include treatments in which only sperm are handled (i.e., IUI) or ovarian stimulation without egg retrieval
In Vitro Fertilization (IVF)
Basic Procedure:
• Sperm and eggs are combined in laboratory dish
• IF fertilization occurs, embryos are transferred to uterus where one or more may implant and develop
First “test tube” baby born in 1978 in Britain (Louise Brown)
• First IVF baby born in US in 1981
• In US, ART babies represent approximately 1% of all births
IVF Steps
- Controlled ovarian stimulation
- Prevention of premature ovulation
- Egg retrieval
- Fertilization
- Embryo culture
- Fresh embryo transfer
- Controlled ovarian stimulation
• High doses of FSH for 10 days in early to mid-follicular phase
• Transvaginal ultrasound and blood estradiol (E2) are used to determine when follicles are appropriate for egg retrieval
o Large antral follicles secrete E2 but sustained elevated E2 can stimulate LH surge
* multiple follicles on both ovaries
* developing follicles are drawn from cohort targeted for that month (# in cohort declines with age)
**goal is 8-15 good follicles
- Prevention of premature ovulation
- GnRH anatagonist
• administered in late follicular phase
• Blocks action of GnRH on gonadotrope secretion of LH (&FSH) to prevent LH surge
• Immidiately inhibit LH (&FSH) production and secretion - GnRH agonist (Lupron) can also be used to prevent early ovulation
• Initially (last 10 days of luteal phase prior to ovarian stimulation) stimulates pituitary glas to release all stores gonadotropins (LH & FSH)
• Then (first 10 days of follicular phase), GnRH agonist suppresses production of new LH & FSH
- Egg Retrieval
- hCG- administered approximately 34 h prior to retrieval
* Transvaginal ultrasound aspiration is minor outpatient surgery
- Fertilization
- Standard IVF
- MII oocytes are placed in culture medium
- Motile sperm introduced to oocytes and stored in incubator where fertilization occurs within 24 h
- Intracytoplasmic sperm injections (ICSI)
- Used when rates of fertilization are expected to be poor (i.e., oligospermia)
- Single sperm injected directly into oocyte
- Bypasses sperm capacitation process
- Embryo Culture
Retrieval (unfertilized oocyte (MII) with polar body) –> 16h –>
Fertilized oocyte with 2 pronuclei (Day 1)
–> 2 days –>
Cleaved embryo (8-cell stage) (Day 3)
–> 2-3 days –>
Blastocyst (Day 5)
- Fresh Embryo Transfer
One of more of embryos is suspended in culture medium and transferred to uterus with a catheter
• Embryos usually transferred on either culture day 3 or day 5
• The number of embryos transferred is at the discretion of the doctor
• Extra embryos may be cryopreserved (frozen) and stored for future transfer (frozen embryo transfer)
IVF Cycle Summary
Days 1- 13: Follicular Phase • Days 3-12: FSH • Days 9-12: GnRH antagonist • Days 3, 7, 10, 14: U/S and E2 • Day 12: hCG trigger Day 14: Retrieval Days 15-28: Luteal Phase • Days 14-28 Progesterone (continue to end of 1st trimester if pregnant) • Day 19: Transfer
Frozen Embryo Transfer
- Day 28: Pregnancy test
- Permits additional attempts at pregnancy, siblings
- First frozen embryo baby born in 1983
- Also allows use of “adopted” embryos (donated by a couple who becomes pregnant and no longer needs/wants extra embryos)
Donor Eggs
- Likelihood of live birth is determined by age of woman who produced egg (not the birth mother)
- Egg donors are typically in their 20’s
- Recipient candidates include women who are older, have diminished ovarian reserve, or have or are carriers of genetic abnormalities (e.g., Turner’s syndrome- XO genotype, ovaries do not develop)
- In 2011 average success rate for donor eggs was 56%
Donor Egg Cycle Summary
Days 1- 13: Follicular Phase • Days 3-12: FSH (DONOR) • Days 9-12: GnRH antagonist (DONOR) • Days 3, 7, 10, 14: U/S and E2 (DONOR AND RECIPIENT- only 3 and 12) • Day 12: hCG trigger (DONOR) Day 14: Retrieval (DONOR) Days 15-28: Luteal Phase • Days 14-28 Progesterone (continue to end of 1st trimester if pregnant) (RECIPIENT) • Day 19: Transfer (RECIPIENT • Day 28: Pregnancy test (RECIPIENT)
Surrogacy
- Traditional surrogate
• Surrogate is inseminated with sperm from male or infertile couple (no IVF involved)
• Surrogate is geneticall related to child - Gestational Carrier
• Carries embryo created by egg and sperm of 2 other individuals (requires IVF)
o Intended mother provided egg
o Intended father provides sperm
o Embryo is transferred to gestational carrier
• Gestation carrier is not genetically related to child
