Exam 3 - Infertility, ART, and Stats Flashcards
What is the definition of infertility? What percent of the population is affected?
inability to achieve pregnancy after 12 months of unprotected intercourse
12% of the reproductive age population
What percent of cases are female factor? What are some female factors of infertility?
40-50% of cases
Ovulatory dysfunction * Tubal factor * Endometriosis * Advanced maternal age * Polycystic ovary syndrome (PCOS) * Luteal phase defect * Toxic insult * Uterine abnormality * Genetic disorder (e.g., Turner syndrome) * Infection
What percent of cases are male factor? What are some male factors of 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
What percent of cases have combined male and female factors?
30%
What percent of cases are idiopathic? What does that mean?
20%, infertility is unexplained
What two ways can female fertility be assessed?
Day 3 Labs, and Hysterosalpingogram (HSG)
Explain how Day 3 Labs can be used to assess female fertility
FSH measured on Day 3 of menstrual cycle
AMH can be measured on any day of the cycle
What do the different levels of FSH on Day 3 indicate?
Explain the level seen in the postmenopausal stage.
Follicular: 2.5 – 10.2
Midcycle: 3.4 – 33.4
Luteal: 1.5 – 9.1
Pregnant: < 0.2
Postmenopausal: 23.0 – 116.3 (follicle depletion means less E production, and stimulation of more FSH)
What do the different levels of AMH on Day 3 indicate?
Infertile: < 0.8
Low fertility: 0.8 – 2.0
Normal fertile range: 2.0 – 6.0
Polycystic Ovarian Syndrome: > 6.0
high levels indicate more pre-antral follicles, low indicates follicle depletion
What D3 FSH and AMH levels indicate a poor prognosis?
FSH >10 and AMH <0.8
What is a hysterosalpingogram, and what will it show in regards to assessing fertility?
xray with contrast dye to determine i the tubes are open or blocked
if the dye is diffuse at the fimbriae, the tubes are normal
if the dye is not spreading that indicates the tubes are not open
How is male fertility assessed? What are the normal ranges for the various parameters?
semen analysis to assess if the sample is sufficient for natural conception
volume >2 mL
liquefaction <60 minutes
viscosity moderate to low
concentration >20 million
motility >50%
morphology >15%
What are oligospermia and azospermia?
oligospermia is <20 million
azospermia is no sperm in the ejaculate
How are most infertility cases treated? What are some examples?
85-90% treated with conventional medical therapies such as dietary modification, exercise, medication, or surgery
ex:
progesterone to treat luteal phase defect
metformin and exercise for PCOS
fertility drugs for ovulation induction (used for IUI)
surgical removal of uterine polyps or septum
What is a polyp vs a septum and why do they cause infertility issues?
polyp- noncancerous growth attached to the endometrium that extends into the uterine cavity
septum - wedge like partition within the uterine cavity
polyps can irritate the endometrium causing inflammation that prevents implantation, and the septum doesn’t have vascularization so they embryo can’t survive if it lands there
What medication can we use to prevent follicle atresia, and when should it be administered?
FSH, given days 5-10
What is the goal of IUI? What are the 4 main components?
goal: to get 2-3 good follicles
- controlled ovarian stimulation
- transvaginal ultrasound
- trigger ovulation at the appropriate time
- intrauterine insemination
What are the goals of ovarian stimulation for IUI?
increase FSH and LH secretion during the early mid-follicular phase
stimulate follicle growth
permit more than one follicle to mature/rescue follicles from atresia
What medications can be used for ovarian stimulation during IUI? What do they each do?
clomiphene citrate (Clomid):
estrogen antagonist blocks negative feedback increasing FSH and LH secretion, may change quality of cervical mucus/endometrium
letrozole (Femara):
aromatase inhibitor, prevent ovarian conversion of androgens to estrogens, lower E permits more FSH and LH secretion (can also impact endometrium but less impact)
follicle stimulating hormone (FSH):
directly stim. follicle development, low doses (75 IU for 3 days), stimulates growth of 2-3 follicles, some brands are purified from menopausal females but others are recombinant hFSH
How is FSH different from clomid or femara in ovarian stimulation?
it is injected instead of an oral pill
must be injected because it is a glycoprotein and would be digested if it was taken orally
What is the purpose of transvaginal ultrasound during IUI?
determine number and size of lead follicles
cancel the cycle if there are too many
On transvaginal ultrasound, what are the ideal conditions for LH surge/ovulation to be triggered?
lead follicle will be 15-18 mm
endometrium will be 6-10 mm thick
Explain how ovulation is triggered for IUI? How long after the trigger does ovulation occur?
mimic the LH surge to stimulate ovulation
hCG (purified from urine of pregnant females or recombinant hCG) because it is structurally like LH but has a longer half life
ovulation occurs approx. 36 hours after the hCG injection
Explain the actual IUI step of the IUI process. What is placed into the uterus?
washed sperm (to remove prostaglandins) are placed in the uterus by catheter just prior to the expected time of ovulation
Summarize the IUI cycle
patient calls with Day 1 of their menstrual period
E2 antagonist, aromatase inhibitor, and FSH given days 3-7
ultrasound day 10
hCG trigger day 12
IUI day 14
pregnancy test day 28
Explain the success rates of IUI
max 20% pregnancy rate for females <24, declines to only 3% for females >43
What is ART?
any procedure where both sperm and oocytes are handled outside the body
What is the basic IVF procedure? How many babies are ART births each year?
sperm and egg are combined in a laboratory dish, and if fertilization occurs, the embryos are transferred to the uterus where one or more may implant and develop
2% of all births are ART babies
Describe the first IVF success, the first in the US, and who was the doctor who recieved a Nobel Prize for IVF?
Louise Brown, first test tube baby born in Britain in 1978
First IVF baby in the US was born in 1981
Robert G Edwards won the Nobel Prize in 2010
What is the main goal and the 7 steps of IVF?
goal: 8-15 good follicles
- controlled ovarian stimulation
- prevent premature ovulation
- trigger LH surge when appropriate
- egg retrieval
- fertilization
- embryo culture
- fresh embryo transfer
What is the process of controlled ovarian stimulation for IVF?
High doses of FSH (225 – 300 IU) for 10 days
in early to mid-follicular phase
Transvaginal ultrasound and blood
estradiol are used to determine when
follicles are appropriate for egg retrieval
What medications can prevent premature ovulation and when should they be given? What do they do?
GnRH antagonist:
administered in the late follicular phase, blocks the action of GnRH on secretion of FSH and LH to prevent the LH surge, inhibits LH and FSH immediately
GnRH agonist: (Lupron)
given for the last 10 days of the luteal phase prior to ovarian stimulation and the first 10 days of the follicular phase
in luteal phase- stimulates pituitary gland to release all stored FSH and LH
in follicular phase - down regulates the GnRH receptors which suppresses the production of FSH and LH even if there is GnRH present
On transvaginal ultrasound, what are the ideal conditions for final maturation of the oocyte/egg retrieval?
Lead follicle will be about 18 mm
Endometrium will be about 10 mm thick
In IVF, which medications can be given to trigger LH surge?
GnRH agonist (but not if they have been using it to suppress ovulation)
or hCG
Describe egg retrieval for IVF?
retrieval occurs about 34 hours after ovulation trigger (hCG or GnRH agonist)
transvaginal ultrasound aspiration under anesthesia is a minor outpatient surgery
Describe the two methods of fertilization for IVF
Standard in vitro fertilization (IVF) - M2 oocytes are placed in culture medium, motile sperm are introduced to oocytes and stored in an incubator where fertilization occurs within 24 h
Intracytoplasmic sperm injection (ICSI)- Used when rates of fertilization are expected to be poor
What does ICSI bypass in the normal fertilization process?
sperm capacitation, natural selection of the “best sperm”
Describe the development of an embryo in culture from retrieval to day 5
retrieval: unfertilized M2 oocyte with polar body
day 1, 16 hours after retrieval: fertilized oocyte with 2 pronuclei
day 3: cleaved embryo (8 cell stage)
day 5: blastocyst undergoes assisted hatching
Describe fresh embryo transfer for IVF
one or more embryos are suspended in culture medium, transferred into the uterus with a catheter
embryos are usually transferred on day 3 or day 5
number of embryos transferred is at the discretion of the doctor
After embryo transfer, what medication should a woman take? Why? When does she stop taking it?
progesterone, because egg retrieval destroys the follicle and prevents the corpus luteum from forming
if pregnant, continue for 10 weeks
if not pregnant, can stop after pregnancy test
Summarize the IVF cycle using a GnRH antagonist to prevent ovulation
patient calls with day 1 of menstrual cycle
FSH days 3-12
GnRH antagonist days 9-12
ultrasound and estrogen days 3, 7, 10, and 12
hCG or GnRH agonist trigger day 12
retrieval day 14
progesterone day 14-28 (continue to end of first trimester if pregnant)
transfer day 19
pregnancy test day 28
Summarize the IVF cycle using a GnRH agonist to prevent ovulation
GnRH agonist given from day 21 of previous cycle to day 12 of the transfer cycle
FSH days 3-12
ultrasound and estrogen days 3, 7, 10, and 12
hCG trigger day 12
retrieval day 14
progesterone day 14-28 (continue to end of first trimester if pregnant)
transfer day 19
pregnancy test day 28
Summarize the success rates of IVF in comparison to those of IUI
highest rate of success is 45% for <35 (compared to 15% for IUI)
drops to about 8% for >42 (compared to 3% for IUI)
What are the benefits to frozen embryo transfer?
- extra embryos created can be cryopreserved and stored for future use
- permits additional attempts at pregnancy/siblings
- first frozen embryo baby was born in 1983
- also allows use of adopted embryos
What two ways does a patient need to be prepared for FET?
prevent follicle development and ovulation and prepare the ideal endometrium
What medication can be used to prevent follicle development and prepare the endometrium for a FET?
estradiol
When should a woman doing a FET start progesterone?
day 14
When should a blastocyst embryo be transferred for a FET? Why?
day 19 (day 14 start progesterone+the 5 days the embryo would have been developing before it reached the uterus)
Summarize a FET cycle?
patient calls with day 1
estrogen days 3-28
ultrasound days 3, 12
progesterone days 14-28
transfer day 19
pregnancy test day 28
continue estrogen and progesterone through end of first trimester if pregnant
Why is FET better than fresh embryo transfer?
allows time for genetic testing,
better endometrial receptivity (ability to attach to the blastocyst and keep it alive) after a “normal” cycle
Summarize the success rates of FET IVF vs. fresh IVF
almost 50% success in <35 (compared to 45% in fresh IVF)
almost 30% success in >42 (compared to 8% fresh IVF)
slower drop off with age
Regarding egg donation, who would donate eggs, who would receive them, and what determines the likelihood of a live birth?
egg donors are typically in their 20s
recipients include women who are older, have diminished ovarian reserve, or have a genetic abnormality like Turner’s syndrome (XO, no ovaries)
likelihood of live birth is determined by the age of the woman who donated the eggs at the time of the egg donation
How do the percent of cycles that end in a live birth differ between patient eggs/embryos and donor eggs/embryos?
donor eggs and embryos are always a bit higher, but they also don’t drop off near as much with age
Summarize the donor egg cycle (for the donor patient)
patient calls with day 1
FSH days 3-12
GnRH antagonist days 9-12
ultrasound and estrogen levels checked days 3, 7, 10, and 12
hCG trigger day 12
retrieval day 14
Summarize the donor egg cycle (for the recipient)
patient calls with day 1
estrogen days 3-28
ultrasound days 3, 12
progesterone day 14-28
transfer day 19
pregnancy test day 28
continue estrogen and progesterone until end of first trimester if pregnant
What are the two types of surrogacy? What is the difference between them?
traditional surrogate - surrogate is inseminated with sperm from the male partner and the surrogate is genetically related to the child
gestational carrier -
carries the embryo created from the egg and sperm of two other people (requiring IVF), carrier is not genetically related to the child
Describe the age breakdown of the patients using ART?
over 1/3 are <35, about 1/4 are 35-37, and 20% are 38-40. The last 20% is about equally 41-42 and >42.
How do the values of cycles started, retrievals, transfers, pregnancies, and live births differ from each other?
86,000 cycles started
76,000 retrievals
53,000 transfers
24,000 pregnancies
19,000 live births
How can pregnancy be confirmed? When can each of these be done?
chemical pregnancy: positive hCG blood test at 4 weeks gestation
clinical pregnancy: chorionic sac present at 5-7 weeks gestation, or detection of a heartbeat at 7 weeks gestation
What are the three main ways that pregnancies end other than live birth?
miscarriage (spontaneous abortion)
induced abortion
stillbirth
2020 ART data will not be published until…beacause…
late 2022
any cycle that started in Dec. 2020 will not have a final result (possible live birth) until mid 2021, then it takes about a year to compile and publish data
As age increases, how does rate of pregnancy loss change?
rate increases from 13.6% (under 35) to 36.5% (41-42)
even though the percent of pregnancies lost appears to be lower, those numbers represent the percent of pregnancies lost out of all cycles started (which is much higher for <35)
really, you have to compare the number of pregnancies lost/number of pregnancies, which ends up being a much smaller percentage for women <35 than women age 41-42
If a single embryo transfer results in twins, what kind of twins are they?
identical, because one embryo must have split into two fetuses
Why are more embryos transferred to older women?
pregnancy rates are so low that the chance of both implanting is much less likely
What are the arguments FOR transferring more than one embryo at once?
increases live birth rate by 6.2% (so you are a little more likely to become pregnant)
What are the arguments AGAINST transferring more than one embryo at once?
increases chance of twins (or more) by 39.2%
In a multiple gestation, what are some potential complications for the fetus and mother?
fetus:
preterm birth, death within 1 month, prematurity, IUGR, intrauterine death of one or more fetuses, miscarriage, congenital anomalies, lifelong disability
maternal:
preeclampsia, premature labor/prolonged bedrest, placental abnormalities, maternal hemorrhage, gestational diabetes, anemia, excess amniotic fluid, C section
Why did Dr. Kamrava lose his medical license?
transferred 12 embryos to a patient, 8 implanted and octuplets were born at 30.5 weeks weighing between 1 lb 8 oz and 3 lb 4 oz
Who is baby boy Curtis? What is his story and why is it so controversial?
youngest surviving preemie, born at 21 weeks and 1 day weighing 14.8 oz
Was discharged from the hospital after 275 days
Babies born at less than 23 weeks/400 grams are not considered viable
At 22 months old, he is down to one medication for blood pressure, 2 inhalers, and can be unhooked from oxygen for an hour a day
How many infants from multiple births are from ART? How is this data collected? Does that mean most (87%) of multiple gestations are occurring naturally?
13% of multiple gestations are ART
number of multiple infants from ART / number of multiple infants total = % multiples from ART
Other 87% are not necessarily natural conception, because IUI does not count as ART
How do non-ART treatments and delayed childbearing increase twinning rates?
fertility medication, IUI, etc. can increase twinning rates by increasing the potential number of oocytes ovulated
contributes approx. 72%
FSH increases with age which might cause more than one oocyte to ovulate (resulting in twins more often, dizygotic)
contributes approx. 28%
What is SET? Why is it good to see an increase in SET?
single embryo transfer, increases likelihood of single gestations
What is multifetal pregnancy reduction and why is it offered? How can it be avoided?
first trimester or early second trimester procedure to reduce the number of fetuses in a multiple gestation by one or more (most cases involve 3+ fetuses)
there is a risk of spontaneously losing the entire pregnancy, which has to be weighed against the risks of the multiple gestation itself
can be avoided by transferring one embryo at a time and not doing IUI cycles with too many follicles
What percent of ART uses donor eggs? Why are older women more likely to use donor eggs?
donor eggs/embryos used in approx. 9% of cases, but increases sharply for women over 40. 68% of cycles in women over 48 used donor eggs, likely because they cannot produce their own eggs.
Why is it difficult to know how many children are conceived from donor sperm?
No national data for babies conceived using donor sperm
