Infertility Flashcards
What is infertility?
The inability to conceive after 1 year of unprotected intercourse
What are the two types of infertility?
Primary infertility: couple has never conceived a child
Secondary infertility: couple is previously successful in conceiving but unable to acheive a subsequent pregnancy
What is the impact of infertility on couples?
Emotionally and psychologically difficult (anger, sadness, jealousy, guilt)
Impacts relationships
When should infertillity be investigated?
Woman under 35, and after 12 months of unprotected intercourse
Earlier investigation is appropriate in the following groups:
- Age over 35
- Menstrual abnormality
- Previous urogenital surgery
- History of pelvic disease and STIs
- Abnormal genital exam
Initial male infertility evaluation is non-invasive
What are some risk factors for female factor infertility?
Increasing age
Ovulatory dysfunction
- Anovulation
- PCOS
- Luteal phase defect
Anatomical factors
- Tubal dysfunction
- Cervical factors
Why is increased age a risk factor for infertility?
Increased exposure to development of disease (ex. endometriosis, PID)
Ovulation becomes more irregular
Fewer eggs, lower quality eggs remain
What causes anovulation?
Occurs as a result of disruption of the hypothalamic-pituitary-ovarian (HPO) axis
- Physical injury to hypothalamus or pituitary
- Obesity, anorexia, bulimia
- Excessive exercise
- Stress
- Exposure to chemo/rad
- Endocrine disorders (diabetes, thyroid, hepatic disease)
What are some diagnostic criteria PCOS?
- Hypogonadism
- Ovulatory dysfunction
- Polycystic Ovaries
Need 2-3 symptoms to diagnose
What causes PCOS to develop?
Peripheral insulin resistance leads to hyperinsulinemia and stimulation of excess ovarian androgen production
What are some signs of PCOS?
Menstrual irregularities (amenorrhea or oligomenorrhea)
Hyperandrogenism (hirsutism, acne, alopecia)
Overweight/Obesity (60-70%)
Infertility (70%)
What are some conditions that are associated with PCOS?
Reproductive challenges
- Infertility
- Pregnancy complications
Endometrial hyperplasia or cancer
Metabolic issues
- DM
- CVD
- Metabolic Syndrome
Obstructive Sleep Apnea
Depression
What are the goals of treatment for PCOS?
- Reduce or eliminate hyperandrogenic features
- Manage underlying cardio metabolic abnormalities
- Prevent endometrial hyperplasia due to chronic anovulation
- Contraception for those not wanting pregnancy
- Ovulation induction for pregnancy
What are the treatment options for PCOS?
1st line: weight loss for overweight women
- Improve fertility, help with hirsutism, can help with BG, BP. lipids
2nd line: pharmacotherapy
3rd line: bariatric surgery
What are some treatment options for menstrual cycle irregularities with PCOS?
1st line: CHCs (oral route preferred, start with low dose estrogen and progestin with low androgenicity, assess for VTE risk)
- Regulate menstruation
- Protects against endometrial hyperplasia
- Helps androgenic symptoms
Alternatives:
- Progestin-only therapy (LNG IUS, cyclic progestins, progestin-only pill)
- Metformin (off-label use, improves glucose tolerance, reduced androgen production in ovaries)
What are some treatment options for hirsutism in PCOS?
1st line: CHC (oral preferred, try for 6 months before moving on)
2nd line: antiandrogen (spironolactone & finasteride)
3rd line: Eflornithine cream (directly inhibits hair growth)
Non-drug: laser treatment, electrolysis, waxing
What are some treatment options for acne in PCOS?
1st line: CHCs (particularly low androgen progestins)
Topical acne medications
Consider spironolactone
What are some pharmacological treatment options for improving fertility in women with PCOS?
- Letrozole (1st line drug option)
- Clomiphene citrate
- Metformin
What is the MOA of letrozole in treatment of infertility in women with PCOS?
Aromatase inhibitor (off-label use to help with anovulation)
By supressing aromatase, estrogen also falls. Lower estrogen levels promote production of FSH, which stimulates ovarian follicles to develop and mature
70-80% of patients will ovulate and a pregnancy rate of 30%
What is the dosing for letrozole?
Take 2.5mg for 5 days during either days 3-7 or days 5-9 of the menstrual cycle
What are some side effects associated with letrozole?
Hot flashes
Fatigue
Nausea
Multiple births (twins)
What is the MOA of clomiphene citrate for treatment of infertility among women with PCOD?
It is a SERM and blocks estradiol receptors in the hypothalamus which allows for FSH release and subsequent follicular stimulation and ovulation
How is clomiphene citrate dosed to induce ovulation in women with infertility due to PCOS?
take 50mg daily for 5 days staring on day 5 of the menstrual cycle or at any time if amenorrheic
What are some adverse effects associated with clomiphene citrate?
Multiple gestations (higher risk vs. letrozole)
Hot flashes
Abdominal discomfort
Vision disturbances
CI in pregnancy just like letrozole
When are letrozole and clomiphene expected to induce ovulation?
5-10 days after the last dose
Letrozole is more effective for acheiving live birth in patients with ovulatory disorders
What is the optimal timing for intercourse to maximize chances of becoming pregnant?
4-5 days prior to ovulation and every 24-48 hours (ensure ejaculate volume and healthy sperm)
What is the utility of metformin on treating infertility in women with PCOS?
Works by helping reduce weight and improves cycles by regulating the insulin component of PCOS
What is the dosing for metformin for treatment of infertility in women with PCOS?
Start with 250-500mg, and gradually increase
Can d/c once pregnancy acheived in women with no history of T2DM
What is luteal phase defect?
Insufficient progesterone levels do not allow for the preparation of the endometrium for implantation
Difficulty acheiving or maintaining pregnancy
How is luteal phase defect treated?
Progesterone is used for luteal phase support
What are some causes for blocked fallopian tubes resulting in infertility?
Endometriosis
Pelvic inflammatory disease (PID is a serious complication of some STDs)
What are some treatment options for infertility-associated endometriosis?
- NSAIDs for pain relief
- Watchful waiting
- Conservational surgery (remove surface endometriosis)
- Ovarian stimulation or in-vitro fertilization
What are some causes of male factor infertility?
Unknown (40-60%)
Obstructive/physical/genetic factors
Sexual intercourse factors
Endocrine factors
Gonadotoxic (sperm) factors
What are some obstructive factors that can cause male factor infertility?
- Trauma
- Surgery (abdominal, prostate, others)
- STIs
- Cystic fibrosis
- Klinefelter syndrome
What are some sexual intercourse factors that are linked with male factor infertility?
Decreased libido
Erectile dysfunction
Impaired ejaculation (retrograde)
What are some endocrine factors associated with male factor infertility?
Obesity
Hypothalamic or pituitary dysfunction alters the secretion of FSH, LH, and testosterone
What are some sperm factors that can affect male fertility?
Environmental:
- Alcohol, cigarette, excessive heat, radiation, toxin exposure
Drug-induced:
- Marijuana, cocaine, chemo, steroids, finasteride, spironolactone, nitrofurantoin
What are some treatment options for male factor infertility?
Correct modifiable risk factors
Surgical repairs (varicoceles, obstructive lesions)
Hormone therapy (gonadotropins or pulsatile GnRH)
Sperm cryopreservation (done before cancer therapies)
Assisted reproductive technologies
What are some devices used to aid fertility?
Basal Body Temperature (BBT) charting
Ovulation prediction kits
How does maternal age affect IVF success?
Steady decline after the age of 35
Why is infertility becoming more common?
Increased maternal age
Starting families later (higher education, costs associated with child-rearing)
People talk about it and share (less taboo now)
What is involved in ovulation induction (OI)?
Letrozole or clomiphene therapy
Timed intercourse
With or without trigger shot (to help with oocyte retrieval)
What is superovulation (SO)?
Ovaries are stimulated with hormones to produce follicles
Goal is to produce 2-4 eggs
Combined with IUI
Medications used for SO and IVF are the same, but doses are lower in SO
What is intrauterine insemination (IUI)?
Insert sperm directly into the uterus
Sperm is prepped (separated in centrifuge, evaluated and washed)
Can be done +/- superovulation
What is intra-cytoplasmic sperm injection (ICSI)?
Inject the sperm directly into the egg (done in a lab)
May be used for low sperm count, impaired sperm penetration, anti-sperm antibodies, previous IVF failure)
List the steps involved in in-vitro fertilization (IVF)?
Tests & Diagnosis
Ovarian Stimulation & Control
Egg Retrieval
Sperm Collection/Retrieval
Fertilization
Transfer
Pregnancy Test
Review slides 70 and 71 for an overview of hormones in IVF
How are ovaries stimulated in IVF?
Estrogen and progesterone are monitored for 8-14 days
FSH and LH analogues are administered (urinary or recombinant sources)
Review slide 74 for comparing urinary and recombinant analogues of FSH and LH
How is premature ovulation prevented to ensure multiple follicles mature at the same time?
GnRH agonists (leuprolide)
- Induce release of large amounts of FSH and LH
- Used for 7-10 days to see downregulation of GnRH receptors
OR
GnRH antagonists (ganirelix)
- prevent endogenous pulses of FSH and LH
Review slide 79 for GnRH anatagonist protocol for IVF
What are some risks associated with ovarian stimulation?
Ovarian Hyperstimulation Syndrome (OHSS)
Ovaries can enlarge, and is very painful and can result in permanent damage to ovary
Need to monitor patient
Can be avoided by limiting the amount of stimulation and expected number of eggs to be harvested
What is involved in oocyte retreival in IVF?
A trigger shot (HCG) is given to mature oocytes to encourage ovulation of mature oocytes
Retrieval occurs 34-26h after trigger shot (timing is of the utmost importance)
Transvaginal ultrasound guided needle aspiration to extract eggs
Ideally retrieve several (10-12) well developed oocytes
Progesterone is given for luteal phase support. This promotes the endometrium to become more hospitable to embryo implantation
What is involved in sperm collection/retrieval in IVF?
Collect fresh sperm (ideally obtained on day of oocyte retrieval)
Retrieval may be considered if pt has obstructive issues, non-obstructive issues, neurological injury, retrograde ejaculation
What is involved in the fertilization & culture step of IVF?
Fertilization occurs within 18-24h of exposing oocyte to sperm
Oocytes and sperm are assesed and evaluated
Once fertilization has occurred, embryos are transferred to a growth medium and incubated
What is involved in the transfer step in IVF?
Transfers occur on Day 2 (embryo transfer) or Day 5 (blastocyst transfer)
Usually 1-2 embryos/blastocysts are transferred
Number of embryo/blastocysts transferred depends on previous pregnancies, maternal age, and medical history
Review slide 89 for overview of IVF process
What are some side effects associated with IVF?
Headache
Mood changes
Injection site discomfort
Hot flashes
Breast tenderness
See slide 91
What are the success rates for infertility treatments?
60-70% of couples treated for infertility end up with a healthy child
