Repro 1 Human Reproduction Flashcards
Theca Cells
works in a complimentary fashion with Granulosa Cells
►Pre-Ovulation
– Produce androstenedione (intermediate)
►Post-ovulation
– Produce Progesterone
Granulosa Cells
works in a complimentary fashion with Theca Cells
►Pre-Ovulation
– Imports Androstenedione from Theca Cells and uses it to produce Estradiol / Estrogen
►Post-ovulation:
– Produce Progesterone
Luteal Cells
Post-ovulation: theca and granulosa cells become LUTEAL cells
– Produce Estrogen & Progesterone
What are the steroid produces of the ovaries?
Androstenedione
Estrogen
Progesterone
Ovarian Cycle
endometrial cycle
►Ovarian Cycle: • Concerned with maturing an oocyte and its ovula=on. – follicular – ovulation – luteal
►Endometrial cycle • Concerned with crea=ng an environment that nurtures fertilized ovum. – proliferative – secretory – atretic
How many follicles does a baby girl have?
- From birth onwards, primary follicles undergo apoptosis
- At birth, ~2 million follicles
- By puberty, ~400 000 remain
- Average woman will ovulate 500 times
Elegant Strategy
…vs..
Siege Strategy
Elegant Strategy
–female cycle!
Siege Strategy
– for every heartbeat, males produce 1000 sperm
Early Ovarian Follicular Phase
Primary follicles respond to increasing FSH levels; developing theca and granulosa cells.
►LH promotes:
theca cells = androstenedione
►FSH promotes:
granulosa cells = estradiol
What does Estradiol promote?
Estradiol promotes: • granulosa cell proliferation • estrogen receptors • FSH receptors • LH receptors on granulosa cells
Late Ovarian Follicular Phase
- First follicle to develop LH receptors on granulosa cell becomes the DOMINANT FOLLICLE
- Dominant follicle responds to LH with ESTROGEN surge.
What does the Estrogen do?
- estrogen surge has a positive feedback effect on anterior pituitary
- results in LH spike prior to ovulation (IMPORTANT PIECE!)
- Dominant follicle inhibits sister follicles development (paracrine interaction).
Ovulatory Phase
►The surge of LH resulting from estrogens from the dominant follicle is critical for ovulation
►LH surge requires 2 days of elevated estrogen (200 pg/ml).
►LH triggers ovulation by:
• Neutrilized action of oocyte maturation inhibitor
• Induces the enzyme prostoglandin endoperoxidase synthase. Results in prostoglandin, thromboxane and leukotriene production.
• Contraction of follicular wall
Ovarian Luteal Phase
- Occurs post-ovulation
- In response to elevated LH, Granulosa cells and Theca cells form LUTEAL cells (corpus luteum)
- Luteal cells respond to LH by producing PROGESTERONE and estrogen.
- If oocyte (ovum) is not fertlized, luteal cells degenerate after ~12 days
Regulation of Ovarian Cycle
- Cycle is driven by LH and FSH.
- Initial increase in FSH recruits many follicles in both ovaries
- Steroid production begins in Theca cells under the influence of LH
- Granulosa cells on Dominant Follicle start to secrete ESTROGEN
- Increasing Estrogen levels POSITIVE FEEDBACK on ant. pit. Resulting in an LH surge (necessary for ovulation).
Endometrial Cycle
►Proliferation Phase
Cells lining the uterus divide in response to estradiol from granulosa cells, forming a layer of glands and blood vessels
►Secretory phase
After ovulation, cell division halts. Progesterone augments the blood supply and initiates the secretion of acid mucin
►Atretic phase
In the absence of a fertilised oocyte, progesterone decreases resulting in a loss of the uterine lining. This produces bleeding for 2-4 days. The next cycle begins on day 1 of bleeding and is marked by an increase in FSH.
When does progesterone go away?
Progesterone goes away in the absence of a fertilization event.
The cycle will begin again …
How long is the luteal phase?
14 days
If a woman has a menstrual cycle of 35 days, how long are the two phases?
Follicular Phases
• 21
• dynamic
Luteal Phase
• 14 days
• fixed!
Where does fertilization actually happen?
Fallopian Tube
How do sperm know what tube to go to?
Sperm have some “chemotactic” sensations that are able to assess which fallopian tube the egg is located. The swim towards that tube.
Follicular Phase
►Follicular phase
• Proliferative Endometrium (endometrial growth)
• Endometrial cell growth estrogen mediated
►Histology:
• Endometrial stroma thickens, glands elongate.
• No crowding
• <50% ratio glands to stroma
Luteal Phase
►Luteal phase
• Secretory endometrium (endometrial stabilization)
• Estrogen and progesterone mediated
►Histology:
• Endometrial stroma becomes loose and edematous.
• Blood vessels become thickened and twisted
• Endometrial glands tortuous
• >50% ratio glands to stroma
How long does sperm live in the female reproductive tract?
About 3 days.
Sperm hangs around for a while
When does basal temperature peak in women?
After Ovulation due to rising Progesterone
increases 0.5 Celsius
stays elevated from post-ovulation to start of menses
Surgery Options of Contraception
Women
…vs…
Men…
►WOMEN: Tubal Ligation
• Several methods availbale
• Older method was very invasive & risky and required General Anasthesia
►MEN: Vasectomy
Options for Contraception
►Natural Methods
►Tubal Ligation
►Barrier Methods
►Hormonal Contraception
“The Pill”
contains combo of estrogen & progesterone
Estrogen goes to Pituitary and causes Negative Feedback. Causes FSH levels to go down
Therefore, a dominant follicle will not be recruited!
Inhibits the production of a dominate follicle
What would happen if a woman just took Estrogen throughout the year as a birth control method?
Continuous proliferation of the lining
Abundant cervical mucus production
RESULT: could cause Endometrial Cancer
What is Progesterone added to the Birth Control?
Progestreone is added to BC becasue it allows:
• only supposed to have estrogen around in luteal phase
suppressess LH release
• thickens cervical mucus (sperm less likely to get though)
• affects the lining
What effect does the Pill have on the uterine lining?
THIN lining
Contraindications to Estrogen
►Blood Clots
►Hx of Breast Cancer
►Liver Disease
Progesterone ONLY pill
MOA?
►Primarily suppresses LH release – prevents ovulation (40%)
►Endometrium not receptive to ovum (decidualized bed with atrophic glands)
►Cervical mucus thick and impervious
►Reduced tubal peristalsis
IUD
►HORMONAL
• Progesterone keeps lining thin.
• Fertilized egg cannot implant.
►NON-HORMONAL
• Copper IUD
• toxic to sperm
• causes low-grade irritation to lining to prevent implantation
The pill is used for LOTS of different things.
What HUGE benefits does it have?
- Decreases risk of epithelial ovarian cancer
* Decrease risk of endometrial cancer
Emergency Contraception
2 different methods
►”Plan B”
• Progesterone blunts the LH surge → prevents ovulation
• thins lining → prevents implantation
• most often done
►Copper IUD
• prevents implantation
• not often done
Ectopic Pregnancy
What is it?
Occurs when a fertilized egg (embryo) grows outside the uterus
Most ectopic pregnancies happen in the fallopian tube (98%), but they can rarely occur in the ovary, abdomen or cervix
Dx - both:
• serum quantitative hCG
• transvaginal ultrasonography (TVUS).
Hx Taking for difficulty getting pregnant
►What are your periods like?
►Are your periods painful?
(dysmenorrhea - endometriosis)
►Do you know if you are ovulating?
(OTC ovulating sticks)
►How are you timing intercourse?
►Are your otherwise healthy?
►Any previous pregnancies?
►Erections & ejaculation?
Ovulating Sticks
(OTC - over the counter)
How do they work?
Measures LH surge
LH surge happens 36 hrs before ovulation occurs.
The urine kits measure LH levels and let patients know when ovulation is imminent.
When the stick is positive, couples are advised to have intercourse that night and the next night to optimize their chances.
Infertility
DDx
►Ovulation problems
(eg Polycystic Ovary Syndrome)
►Female Age
►Male Age (sperm count & mobility)
►Fallopian Tube / Uterine Factors
►Unexplained (1/3 of cases)
Uterine (endometrial Biopsy)
When do we do it?
Rule out the presence of pre-cancerous or cancerous tissue
NOT for infertility
Day 21 Progesterone
Serum progesterone levels rise after ovulation as it is produced by Corpus Luteum
We order it to confirm that the patient is ovulating
Should actually be called a Mid-Luteal Cycle. Should actually be done 7 days before menses.
Day 3 FSH
FSH stimulates the growth of the dominant follicle.
As women get older, it takes more and more FSH from the Ant Pit to stimualte the follicle to grow.
If Day 3 FSH level is high, that is a very significant warning with both ovulation and the receptivity of the uterine lining.
Hysterosalpingogram
X-Ray test
uses contrast which is injected into the uterus and then through the tubes
Confirms patency (openness) of tubes
CT Scan of Pelvis
Hysterosalpingogram is much better imaging tool to determine the status of a pt’s Fallopian tubes
TSH
Must order in pts who are struggling to obtain pregnancy.
Hypothyroidism can cause anovulation. Also, if is CRITICAL that a pregnant patient have a normal TSH!
Who struggles with infertility?
How common us infertility?
VERY COMMON!
►30-34
1/7 couples
►35-39
1/5 couples
►40-44
1/4 couples
Etiology in Couples with Infertility
Where are the problems?
►Male Sperm Problem
1/3
►Tubal/Pelvic
1/3
►Ovulation & Unexplained
1/3
However, what is the BIGGEST factor in infertility?
FEMALE AGE
Women are waiting longer and longer to have their first child. This is a societal problem.
Cumulative Fertility & Maternal Age
Don’t minimize a year. A year is a super long time when you want something really bad. Waiting can be emotionally exhausting!
►age 20-24
86% chance of conceiving within 1 yr
►age 25-29
78% chance of conceiving within 1 yr
►age 30-34
63% chance of conceiving within 1 yr
►age 35-39
52% chance of conceiving within 1 yr
What is the average age of menopause?
50-51
Why does pregnancy loss increase with maternal age
As women get older, it is harder to get pregnant because so many miscarriages occur.
The best eggs are used first. The ones that are used later have been arrested in Meiosis 1 for longer and accumulate for genetic abnormalities.
Chromosomal abnormalities can be present in older eggs. Most die. Trisomy 21 just happens to be a viable aneuploidy.
Couple presents with Infertility
When to investigate?
►When female is < 36 y/o
– After 12 MONTHS of trying.
►When female is 36 to 39 y/o
– After 6 MONTHS of trying.
►When female is >40
– IMMEDIATE investigations (these people do not have time)
What are the basic elements for Fertility
►Ovulation ►Ovarian Reserve ►Patent tubes / normal uterus ►Sperm ►Intercourse – MALE: erectile dysfunction – FEMALE:
What makes progesterone?
Corpus Luteum
We test for progesterone to prove that she ovulated
Ovarian Reserve Testing
How do we test?
We want to know if a woman is running low on eggs. If she is, then there is not much time left.
Period starts on day 1 of cycle
►DAY 3 FSH
<10 IU/I
low FSH means that it is not taking much FSH for the brain to make an egg
►Estradiol
– should be low because there is no dominant follicle yet
– use to confirm that test occurred on correct day (Day 3)
►Anti-Mullerian Hormone
– new test
What will FSH level look like in a post-menopausal woman?
> 40
Super high because the brain is having to push super hard to push out an egg. No longer any negative feedback. The ovaries no longer respond. There is no estrogen. The brain is hollering at the ovaries, but nothing happens anymore
What are reasons for which a female might not ovulate?
►PCOS
►Hypothalamic Hypogonadism
– Ovaries are just fine, this is a brain problem. The brain shuts down LH & FSH as it does not want to ovulate during stressful times
►Hypothyroidism
►Hyperprolactinemia
►Premature Ovarian Failure
How do we establish tubal patency?
Hysterosalpingogram
Must push dye through Fallopian Tubes in order to visualize them. U/S will not cut it.
Endometriosis
End up with big pockets of blood in ovaries
displaced endometrial tissue continues to act as it normally would — it thickens, breaks down and bleeds with each menstrual cycle. Because this displaced tissue has no way to exit your body, it becomes trapped. When endometriosis involves the ovaries, cysts called endometriomas may form.
Male Infertility
Hx?
►Can he have an erection and ejaculate?
►Has he had surgery or infection or injury to his genitals?
►Has he fathered children in the past?
►Does he have any toxic exposures?
– smoke marijuana
Semen Analysis
►Volume
≥1.5 ml
►Concentration
≥ 15 million/ml
►Motility
≥ 32%
►Normal Morphology
≥ 4%
What could be wrong in a couple who has never been able to get pregnant?
Fertilization problem
Implantation problem
Work Up Of Infertility
►MALE:
Semen analysis
►FEMALE – Ovarian Reserve Testing – Day 3 FSH and estradiol/AMH testing – Hysterosalpingogram – TSH and Prolactin – Pelvic ultrasound – Luteal phase progesterone
How common is PCOS?
Extremely common!
PCOS
How do we make a diagnosis?
Need 2 of 3:
►Oligo/Amenorrhea
►Clinical or laboratory evidence of elevated androgens
– higher levels of male hormones → Hirsutism & Acne
►Polycystic ovaries on ultrasound
Oligomenorrhea
What is it?
35 day or longer cycle
PCOS
Why is the name a misnomer?
There are NOT big cysts, they are Antral-follicles
The ovaries are simply full of eggs that have antral follicles than their relative age counterparts.
The ovaries are little bulkier, but not very much.
What must be ruled out?
►Congenital Adrenal Hyperplasia
– 17-0HP blood test
►Cushing’s Syndrome
– Clinical signs and AM
Cortisol
►Hyperprolactinemia
– Galactorrhea and elevated prolactin
►Hypothyroidism
– TSH
PCOS
What do pts complain of?
Infertility (because these pts are not ovulating)
Hirsutism/Male pattern hair loss
Acne
Irregular Cycles
PCOS
What does the pathogenesis involve?
⬆︎LH
⬆︎Androgens
⬆︎Insulin
Starts in the hypothalamus …
• RAPID GnRH pulsatility
• leads to a perferential increase in LH over FSH
• Increased LH causes Theca cells to make androgens preferentially
• Granulosa cells have less FSH and don’t aromatise as much to estrogen
• Elevated local androgens inhibit follicular development
How is Insulin involved in pathogenesis of PCOS?
DIRECTLY:
• works synergistically with LH to increase
theca cell androgen production (higher insulin levels further contribute to androgen production)
INDIRECTLY:
• decreases sex-hormone binding globulin to increase circulating testosterone
Infertility Issues with PCOS
What is the first thing we can suggest?
Lose Weight
• will improve Insulin status
• This might be enough to promote ovulation
What is first line medical Tx for fertility in PCOS patients!
Clomiphene Citrate
- Blocks estrogen feedback at hypothalamus and pituitary (the brain simply can’t “see” the estrogen)
- Causes increased FSH release → kick starts ovulation
(fools the brain into thinking that menopause has arrived… the brain goes “AUGH!” and releases a bunch of FSH & LH)
Clomiphene Citrate
(Estrogen receptor blocker at level of brain, uterine lining)
What are Practical Aspects?
Anti-estrogen effects → thins lining of uterus and thickens cervical mucous
Can cause so much ovulation that a few eggs can get produced → possibility of twins or even triplets!
(could get multiple eggs coming out)
How to get people in regular periods?
►Progesterone Pills for 10 days
Mimic Luteal Phase
►the PILL (but only if pt does NOT want to get pregnant)
Letrozole
Aromatase Inhibitor
- causes the ovaries to make less Estrogen → causes brain to pump out more FSH
Brand new drug for Infertility Tx. We are currently using it off label for this purpose. Will most likely replace Clomiphene within a few years.
Recently shown to work better than Clomiphene
Metformin
MOA?
MOA
- Decreases hepatic glucose production
- Decreases intestinal glucose absorption
- Increases insulin sensitivity
Why Does It Work?
- Reduces insulin levels which decreases the effect of LH on theca cells
Metformin
…vs…
Clomiphene
Metformin gets people to ovulate but not associated with good live birth rates. Metformin is still talked about and used (by older docs) but in reality should not really be used anymore.
Use Clomiphene
What are other options of medical treatment for treating infertility?
►FSH injections
- gets women to ovulate, but not necessarily to pregnancy! - expensive!
- high risk of multiples
►IVF
►Ovarian Drilling
- by burning the ovary, we lower the androgen content in the ovary
- PROBLEM: burn eggs & scar tubes!
- not really used
What if the patient is NOT trying to get pregnant, but is simply presenting with a concern of hirsutism & acne?
- Due to elevated androgens
- Significant patient concern
►Oral Contraceptives
– Estrogen increases SHBG and reduces LH
production
– Progesterone – CAN be anti-androgenic (ex.Diane-35, Yasmin)
►Anti-androgens
– Cyproterone acetate – androgen antagonist
– Spironolactone – antiandrogenic
– Flutamide – anti-androgen
What makes Estrogen?
Dominant Follicle!
What is an important risk of PCOS?
Cancer!
Unopposed Estrogen causes the uterine lining to continue to build up.
Therefore, we need to bring on a period! Women with PCOS need to cycle regularly!
What if the PCOS pt does not want to go on the pill?
At least take 10 days of Progesterone every 3 months to shed the uterine lining!
Which organs contribute to the production of semen?
MOST
● Seminal Vesicles
● Prostate
● Testes → sperm
● Bulbo-urethral Glands
LEAST
What is the “bridge over” water in the male?
vas deferens crossing over the ureter
Spermatogeneis
germ cells
►Spermatogonium 2n ⬇︎ ►Spermatocyte Primary 4n ...then... Secondary 2n ⬇︎ ►Early Spermatid 1n ⬇︎ ►Late Spermatid (DNA torpedoes) 1n
Sertoli Cells
Support Cells
►Sertoli Cells
10% of cells
non-proliferative
support cells
What is the pathway of Sperm OUT of the testis
contents of the seminiferous tubules
⬇︎
“Rete testis” within the mediastinum testis.
Up to 1200 seminiferous tubules combine into this labyrinthine network of collecting chambers, lined with simple cuboidal epithelium.
⬇︎
drain into the efferent ductules and the epididymis.
Epididymis
Function
● Continuous Duct
● Storage & Maturation of Sperm
● Fluid is resorbed
● Spermatozoa mature, gain mobility and fertilizing capacity
● Passage takes about 12 days
● Duct is surrounded by CT & smooth muscle
Where does the vas deferens join the seminal vesicle?
At the ejaculatory duct
vas Deferens
- Hollow tube 40 cm long
- Passes through the iguinal canal, eventually joining the
- seminal vesicle at the ejacualtory duct
- Pesudostratified epithelium (just like epididymis)
- Lamina propria rich in elastic fibres
- triple later muscular wall
- sympathetic stimulation during ejaculation
What happens to sperm after vasectomy?
Spermatozoa are phagocytosed by the principal cells of the vas deferens and epididymis.
Physiology of Erection
Helicine arteries dilate → Vascular sinuses fill → put pressure on veins which are up against tunica albuginea → occuludes vessels → blood does not drain
When do sperm become motile?
Not until they reach the vas deferens
they are still developing as they pass through epididymis
How to treat Infertility?
(1) Lifestyle Modifications
(2) Clomiphine
(3) Clomiphine & Metformin
(4) IVF
What factors must be considered in deciding whether IVF is the treatment of choice for a woman?
- Age
- Ovarian status
- Pre-existing medical conditions
- effect of pregnancy on condition & condition (MEDS) on pregnancy
- Social Issues – financial
- Ethical Issues
How to counsel a women in their 40s about getting pregnant?
Age is not friendly to women who want to reproduce.
The older the patient the less chance there is of conception.
Women in their mid 40s even have a very low chance of successful IVF (very few live births). The uterus is totally good, but the eggs are not. We need an egg donor?
What is the effect of obesity on IVF treatment outcome?
BMI >35 affects treatment outcome significantly
Over 50% will miscarry
Obesity can even induce PCOS
IVF in a Nutshell
- A woman’s ovaries are stimulated with drugs to develop multiple eggs
- When the eggs are ready, they are harvested
- The eggs are inseminated with sperm
- The fertilized eggs are matured into embryos
- One or more embryos are replaced into the uterus
- The extra embryos are frozen for future use.
- Pregnancy test at 2 weeks later to confirm pregnancy
(1) Oocyte Recruitment and Growth
• FSH and LH is administered by daily SubQ injection → promote growth of several ovarian (antral) follicles
(FSH is the true engine)
• Each follicle at maturity will contain 1 oocyte
• Requires between 9 - 12 days before the majority of follicles reach their mature size (17-18 mm in diameter)
• Time to retrieve eggs when several follicles are 17-18mm
• Follicular number and growth is monitored during stimulation using U/S and serum estradiol levels
• Concomitant medication is administered to prevent the developing oocytes from ovulating spontaneously before they can be retrieved.
(2) Triggering of Oocyte Maturity
►When majority of follicles reach their mature size (17-18mm in mean diameter), hCG is administered by SubQ injection
►hCG mimics the biologic effect of LH in the natural menstrual cycle and causes:
– the oocyte to undergo the first meiotic division with extrusion of the first polar body (the oocyte now becomes haploid, i.e. it contains 23 chromosomes – 22 autosomes and 1 sex chr)
– the oocyte to break away from the follicular wall and float freely in the follicular fluid
(3) Oocyte Retrieval
- Oocyte retrieval is performed 34-36 hours after the trigger shot
- Each follicle is aspirated using an aspiration needle connected to a collection tube
- The process is performed vaginally with ultrasound guidance
- An aspiration needle is passed through a needle guide which is attached to the ultrasound probe.
- The needle is advanced through the vaginal wall, into the ovary and then into a follicle.
- The ovary is situated adjacent to the vaginal wall.
- The needle is then passed from one follicle to the next and the fluid from each drained into the collection tube
What is the needle like that is used for egg retrieval?
Needle looks huge & long. However, needs to pass through the U/S probe through the vagina.
The needle itself only goes in just a short distance into the follicle.
The ovary is actually right next to the vaginal wall. (not hanging way out on sideside like in anatomy pics)
(4) Oocyte ID
- Each follicular aspirate is passed to an embryologist in the laboratory for immediate examination.
- When acumulus-oocyte complex is identified (an oocyte surrounded by cumulus cells), some of the excess cumulus is cut away and the oocyte is then placed into oocyte culture medium.
(5) Oocyte Insemination (how the sperm & egg meet)
- Obtain semen sample
- The sperm undergoes a preparation process (swim-up) → select the best!
• Depending on the quality & quantity of the semen the
oocytes are then exposed to the sperm by either
(i) adding many sperm to the culture medium containing each egg (IVF) or
(ii) a single sperm is selected and injected into each egg (ICSI)
When do we actually use ICSI?
“ick-SEE”
• ICSI is employed when sperm quality or quantity is less than ideal and fertilization could potentially be impaired if IVF was used
(6) Oocyte Culture
• The inseminated sperm are placed into an incubator which is strictly controlled for temperature as well as CO2, O2 and nitrogen concentration.
• Fertilization is confirmed by examining each oocyte after 18 hrs. of incubation.
• The presence of 2 pronuclei confirms fertilization.
• The fertilized oocytes are then replaced into the incubator
and grown to either the 3rd or 5th day of development.
• Embryo development is monitored by various means, e.g. by daily examination (appearance/morphology) or by a continuous method (morphokinetics/Embryoscope)
Ideal Embryo Development
►Day 1
• 2 even pronuclei with many nucleoli
• 2 polar bodies
►Day 2
• 4 cells
• even blastomeres
• its way out of the zona pellucida → ready to implant
(7) Embryo Replacement or Transfer
The day of embryo replacement and the number of embryos to be replaced is one of the more controversial issues in IVF today
- Not all embryos have the potential to develop to the 5th day (blastocyst stage) but …
- If an embryo reaches day 5 it has the best chance of implantation and resulting in a clinical pregnancy.
- Many factors influence the decision regarding the number of embryos to replace and the timing of the embryo transfer (e.g. on the 2nd, 3rd or 5th day of development).
- It is always best to balance the chance of pregnancy against the risk of a multiple pregnancy since multiple pregnancy is considered by many as a complication of IVF.
(7) Embryo Replacement or Transfer
Continued …
- Numerous embryo replacement catheters (ERC) have been designed (choice is preferential)
- ERC is passed through the cervical canal under U/S guidance.
- The embryo(s) is/are deposited between 1 and 1.5 cm. from the top of the endometrial cavity.
- The woman receives progesterone either vaginally or IM for support of the luteal phase of the cycle and for a variable length of time afterward depending on whether she becomes pregnant.
- Extra embryos are frozen by vitrification
What is Vitrification?
New process where we freeze something so fast that ice crsytals do not form
How can IVF be used to eliminate disease?
• Pre-implantation genetic diagnosis (PGD)
(single gene defects and chromosomal abnormalities)
• Pre-implantation genetic screening (PGS, CCS)
(recurrent pregnancy loss, recurrent failed implantations of embryos, women over 40 yrs. old)
- Oocyte rejuvenation (ovarian stem cells)
- Embryonic stem cell research
- Gene therapy
How common is IVF?
5 million babies born to date!
Last year, over 1 million were performed in 59 countries
IVF
Can we determine the gender?
No! It is considered a criminal offense
unless for a medical reason like determining male associated diseases
Why do we put more eggs BACK into older patients?
Older patients are more likely to make aneuploidy eggs.
As a result, there is a higher incidence of multiples.
What is the uterine lining like in a woman post-menopause?
Why?
Uterine lining is THIN because there is NO Estrogen
What is the uterine lining like in a woman taking OCP?
Why?
Thin.
Progesterone wins. Progesterone causes the lining to thin.
In PCOS we have elevated androgens due to pulsatile GnRH release which causes a preferential release of LH over FSH.
That said, could we use Anti-androgens to induce ovulation?
YES …. but they are teratogenic.
So we don’t!
What’s going to happen to a PCOS woman who tries an LH ovuation stick?
FALSE POSITIVE!
She already has preferential release of LH over FSH
AMH
Anti-Mullerian Hormone
AMH corresponds to Ovarian Reserve.
If a pt has few eggs, AMH is low.
AMH can be assessed to predict Ovarian Reserve.
Definition of Infertility
Trying for a year
PCOS
What is the affect on the body / risk factors?
Dyslipidemia HTN Cardiac concerns Cancer due to endometrial proliferation Mood issues Sleep Apnea
Varicocele
►Varicocele
“bag of worms”
• dilation of pampiniform plexus of spermatic cord
• affects 15-20% of post pubertal males
• L Tests most common because vein is longer than R. L testicular vein enters the renal vein
• higher intravascular pressure because compressed between Aorta & SMA
• can cause pain or impair reproductive function
• pain increases when standing due to gravity effect
• pain resolves when lying down
• Decreases Sperm count → MOA not clear, but we think testicular veins cool the blood in the testicular artery, helping to maintain the proper temperature for optimal sperm production.
Hydrocele
►Hydrocele
• fluid collection within the tunica vaginalis of the scrotum or along the spermatic cord. These fluid collections may represent persistent developmental connections along the spermatic cord or an imbalance of fluid production versus absorption.
• hydroceles below the age of 1 year usually resolve spontaneously.
• can also be the result of a plugged inguinal lymphatic system caused by repeated, chronic infection of Wuchereria bancrofti
Spermatocele
►Spermatocele
• Spermatic Cyst
• painless, benign fluid filled cysts that are outpocketing of fluid from the epididymis.
• filled with a whitish, cloudy fluid and usually contain sperm
• usually no Sx
• generally just a nuisance
Our PBL couple was trying to have a baby.
Wife had PCOS.
Husband had a varicocele.
What is the workup for varicocele?
►Semen Analysis • volume • sperm morphology • sperm motility • sperm count
►Varicocele Embolization
• U/S guided rerouting of vessels
• relieves that pain and swelling
• MAY improve sperm quality for infertile couples
• wait 2 months before repeating Semen Analysis
The wife had PCOS.
What are treatment options in order of progression?
(1) Lifestyle Modifications – lose weight – timing of intercourse – quit smoking – reduce stress
(2) Clomiphene Citrate
– 8% risk of multiples
(3) Clomiphene Citrate & Metoformin
(4) IVF - In vitro Fertilization
A woman had an abortion in the past.
How do we report this?
Prior Pregnancy Termination
When is meiosis arrested in developing oocyte?
Arrests in Prophase 1 during embryonic development. Thus the older the eggs, the longer they have been arrested in Prophase 1 and the greater the risk of chromosomal abnormalities
Resumes at puberty (whenever that egg gets ovulated). Gets halted again at the metaphase II stage. The arrival of the winning sperm will trigger it to complete Meosis 2. Fertilization that occurs.
Spironolactone
K+ sparing diuretic
Anti-mineralocorticoid
Anti-androgen
What is required to ovulate the mature oocyte?
Androgens
Androstenidione
At ovulation, the egg gets ejected. Where does it go?
Released into abdominal cavity. The fimbrae of the fallopian tube sweep it up and carry it along towards the uterus.
NOTE: Ectopic Pregnancy occurs if that egg gets implanted within the abdominal cavity.
What is Azoospermia?
No sperm in semen
affects 1% of men
The layer of the endometrium that remains to regenerate AFTER menstruation is the:
basal zone.
PCOS
What is the status of each hormone:
• Estrogen
• Progesterone
• Androgen
- Estrogen - normal
- Progesterone ↓
- Androgen ↑
The hormone produced by the corpus luteum which inhibits ovulation is:
Progesterone
What are the products of the second meiosis released from the graafian follicle during ovulation?
secondary oocyte and first polar body
The progressive sequence (with some steps omitted) in the metabolism of steroid hormones is:
Cholesterol ⬇︎ Pregnenolone ⬇︎ Progesterone ⬇︎ Androstenedione ⬇︎ Estradiol (or Testosterone)
In the azoospermic male, the diagnosis of testicular failure can be made by the finding of elevated levels of:
FSH
The Sertoli cells of the testes produce inhibin, which maintains FSH in a normal range. Injury to the Sertoli cells reduce inhibin production, thus permitting FSH levels to rise.
Finding an elevated FSH in men with azoospermia is evidence that the lesion lies within the testes (the brain is “screaming” at the gonads to get busy!
What is the simplest and most accurate test to confirm ovulation?
Mid-luteal progesterone assay
Serum progesterone is simple, accurate, and cheap
- 46 y/o woman
- 35 y/o man
- have had kids together before
- Can’t get pregnant now
Tx?
donor oocyte IVF
Given her age, she likely does not have anymore decent eggs. She needs to be given an egg!
What is the general probability of conceiving during each monthly cycle?
(assuming healthy young couple)
20%
Testicular varicoceles
When should they be repaired?
Should be repaired if there is no other explanation for male factor infertility in association with abnormal bulk semen parameters
In other words, we don’t treat it unless its a problem
Uterine Fibroids
- most common benign tumors in females
- typically found during the middle and later reproductive years
- most are asymptomatic
HOWEVER …
• Can grow and cause heavy and painful menstruation, painful sexual intercourse, urinary frequency and urgency.
• May affect fertility
Uterine Fibroids
Tx?
Hysterectomy
Sx caused by uterine fibroids are a very frequent indication for surgical removal of the uterus
