Fertility (L7)

male infertility MOA

-___________

-sperm function (motility or morphology)

-semen production/transport (blockages)

-ejaculation (ED)

problems with any of these can cause challenges

spermatogenesis

male infertility: HPT Axis

___________ supplies the negative feedback loop and tells the hypothalamus to stop releasing GnRH

testosterone

male infertility: causes of impaired spermatogenesis

secondary: affects the ___________ (hypothalamus or testes)

primary: affects the ___________ (hypothalamus or testes)

hypothalamus, testes

meds associated with male infertility

affecting the HPT axis: anabolic steroids, testosterone (Androgel)

if we are giving extra exogenous testosterone, it can cause too much stimulation of the negative feedback loop and actually cause ___________ testosterone production

decreased

treatment of impaired spermatogenesis

secondary, hypothalamic source: ____________ GnRH

secondary, pituitary source: __________ replacement therapy

GnRH, gonadotropin

treatment of impaired spermatogenesis

primary source: avoid giving _________

testosterone (sooo much T will just shut off the negative feedback loop and the hypothalamus will stop releasing GnRH)

treatment of impaired spermatogenesis

________ source: avoid giving testosterone

primary (i.e. testes)

treatment of impaired spermatogenesis

primary source: avoid giving testosterone

we can give _________ to block the negative feedback path (hypothalamus will just keep producing testosterone since nothing can tell it to turn off)

SERMs

treatment of impaired spermatogenesis

primary source: avoid giving testosterone

we can give _________ to block the conversion of testosterone into estrogen

aromatase inhibitors

treatment of impaired spermatogenesis

primary source: avoid giving testosterone

we can give aromatase inhibitors to block the conversion of testosterone into __________

estrogen

female infertility MOA

fallopian tube: absent or blocked

peritoneal: ____________ or history of PID

uterine: fibroids or polyps

cervix: idiopathic or iatrogenic decrease in receptivity

endometriosis

Polyendocrine Metabolic Ovarian Syndrome (PMOS)

can be caused by genetics, epigenetics, lifestyle

symptoms: hyper___________ (acne, facial hair growth, weight gain, scalp hair loss), _________ disturbances, and _________ issues (increased DM risk d/t insulin insufficiency leads to increased CV risk)

hyperandrogenism, mental, metabolic

PMOS pathophysiology

1. rapid pulsing of _______ causes hypersecretion of _______

GnRH, LH

PMOS pathophysiology

1. rapid pulsing of GnRH causes hypersecretion of LH

2. LH stimulates release of ____________ (FSH would normally promote the conversion of the _________ to estrogen, but this process is inactive in PMOS)

androgens

PMOS pathophysiology

1. rapid pulsing of GnRH causes hypersecretion of LH

2. LH stimulates release of androgens (FSH would normally promote the conversion of the androgens to ____________, but this process is inactive in PMOS)

estrogen

PMOS pathophysiology

1. rapid pulsing of GnRH causes hypersecretion of LH

2. LH stimulates release of androgens (FSH would normally promote the conversion of the androgens to estrogen, but this process is inactive in PMOS)

3. production and release of androgens= increased inhibin= suppressed FSH= increased androgens

4. _________ resistance is exacerbated by increased androgens and causes compensatory hyper__________

insulin, insulinemia

PMOS pathophysiology

1. rapid pulsing of GnRH causes hypersecretion of LH

2. LH stimulates release of androgens (FSH would normally promote the conversion of the androgens to estrogen, but this process is inactive in PMOS)

3. production and release of androgens= increased inhibin= suppressed FSH= increased androgens

4. insulin resistance is exacerbated by increased androgens and causes compensatory _______insulinemia

hyper

PMOS pathophysiology

1. rapid pulsing of GnRH causes hypersecretion of LH

2. LH stimulates release of androgens (FSH would normally promote the conversion of the androgens to estrogen, but this process is inactive in PMOS)

3. production and release of androgens= increased inhibin= suppressed FSH= increased androgens

4. insulin resistance is exacerbated by increased androgens and causes compensatory hyperinsulinemia

5. __________ becomes desensitized to ovarian steroids= loss of _________ _______

hypothalamus, negative feedback

pharmacologic treatment of PCOS

one option: “override the system” by providing exogenous __________ and ___________

estrogen and progestin

pharmacologic treatment of PCOS

one option: “override the system” by providing exogenous estrogen and progestin

_____________________: improves acne and hirsutism, provides menstrual regularity

combined oral contraceptives (OCPs)

pharmacologic treatment of PCOS

one option: “override the system” by providing exogenous estrogen and progestin

combined oral contraceptives: improves acne and hirsutism, provides menstrual regularity

choose a product with _____ estrogen and _____ androgen/progestin

low, low

pharmacologic treatment of PCOS

one option: target the excess androgen production

____________: improved acne and hirsutism, has no effect on menstrual regularity

spironolactone (antiandrogen)

pharmacologic treatment of PCOS

one option: target the excess androgen production

spironolactone: improved acne and hirsutism, but has no effect on _________ __________

menstrual regularity (OCPs or Metformin could help with that)

pharmacologic treatment of PCOS

one option: target the excess androgen production

spironolactone: improved acne and hirsutism, has no effect on menstrual regularity

is this a good option for patients who desire to pregnancy?

NO

pharmacologic treatment of PCOS

one option: target the insulin resistance

__________: improves acne and hirsutism, improves menstrual regularity and ovulation, and may help with weight loss

Metformin

pharmacologic treatment of PCOS

one option: target the insulin resistance

Metformin: improves acne and hirsutism, improves menstrual regularity and __________, and may help with weight loss

ovulation

pharmacologic treatment of PCOS

one option: target the insulin resistance

Metformin: improves acne and hirsutism, improves menstrual regularity and ovulation, and may help with weight loss

is this a good option for patients who desire to pregnancy?

YES!

pharmacologic treatment of PCOS

__________ can be used to lower weight, although there is less data on metabolic and reproductive effects

these drugs are NOT suggested for use in pregnancy

GLP-1s

pharmacologic treatment of PCOS

GLP-1s can be used to lower weight, although there is less data on metabolic and reproductive effects

are these a good option for patients who desire to pregnancy?

NO

ovulation induction: goal is ____________ development (start with the least invasive and simplest treatment option) while minimizing the risk of ovarian hyperstimulation syndrome (OHSS)

monofollicular

ovulation induction: goal is monofollicular development (start with the least invasive and simplest treatment option) while minimizing the risk of ________ _________ _________

ovarian hyperstimulation syndrome (OHSS)

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

oral meds: _______ __________ is selective estrogen receptor modulator that down-regulates estrogen receptors

clomiphene citrate

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

oral meds: clomiphene citrate is selective __________ receptor modulator that down-regulates __________ receptors

estrogen

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

oral meds: clomiphene citrate is selective estrogen receptor modulator that ______-regulates estrogen receptors

down

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

oral meds: ___________ is an aromatase inhibitor that blocks the negative feedback loop by blocking conversion of androstenedione into estrogen

Letrozole

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

oral meds: Letrozole is a __________ inhibitor that blocks the negative feedback loop by blocking conversion of androstenedione into estrogen

aromatase

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

injectables: ___________ creates the LH surge and triggers ovulation

hCG

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

injectables: hCG creates the ____ ________ and triggers __________

LH surge, ovulation

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

injectables: hCG creates the LH surge and triggers ovulation

- finalizes follicular developement

- timed with intercourse/intrauterine insemination

- it is most often used with ___________, but could also be used with oral ovulation induction agents

gonadotropins

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

injectables: gonadotropins (LH/FSH combinations) or hCG (creates the LH surge and triggers ovulation)

SEs: __________ gestations

multiple

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

injectables: gonadotropins (LH/FSH combinations) or hCG (creates the LH surge and triggers ovulation)

SEs: multiple gestations (the highest risk for this is with ____________ )

gonadotropins

ovulation induction: goal is monofollicular development while minimizing the risk of OHSS

injectables: gonadotropins (LH/FSH combinations) or hCG (creates the LH surge and triggers ovulation)

SEs: multiple gestations

serious SEs: ____________ (risk is minimized by monitoring follicle development with ultrasounds and serum estradiol levels)

OHSS (ovarian hyperstimulation syndrome)

OHSS can occur with any ovulation induction medication, but is most common with ____________

gonadotropins

OHSS can occur with any ovulation induction medication, but is most common with gonadotropins

potentially fatal “___-_______” of intravascular fluid (fluid from the veins/arteries goes into the tissues)

3rd-spacing

Assisted Reproductive Technology (ART)

most commonly used is in-vitro fertilization

this is used in patients who have failed _________ _________ with or without intrauterine insemination, or in patients with structural factors (ex: missing or blocked fallopian tubes)

ovulation induction (i.e. pts who fails oral and injectable meds)

Assisted Reproductive Technology (ART)

most commonly used is in-vitro fertilization

1. controlled ovarian stimulation

2. _________ retrieval

3. fertilization in vitro

4. ______ _________ into uterus

oocyte, embryo transfer

Assisted Reproductive Technology (ART)

Controlled Ovarian Hyperstimulation: monitored use of ovulation induction agents to create _______ follicle(s) for IVF

several

Assisted Reproductive Technology (ART)

Controlled OHS: monitored use of ovulation induction agents to create several follicles for IVF

- use of ________ agonists/antagonists to suppress LH

- progesterone support for up to 8 weeks

GnRH

Assisted Reproductive Technology (ART)

Controlled OHS: monitored use of ovulation induction agents to create several follicles for IVF

- use of GnRH agonists/antagonists to suppress ______

- progesterone support for up to 8 weeks

LH (we need to decrease LH surge —> that way we can use hCG to perfectly time our own “artificial” LH surge)

Assisted Reproductive Technology (ART)

Controlled OHS: monitored use of ovulation induction agents to create several follicles for IVF

- use of GnRH agonists/antagonists to suppress LH (we need to decrease LH surge —> that way we can use _________ to perfectly time our own “artificial” LH surge)

- progesterone support for up to 8 weeks

hCG

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

____________: control the onset of menses and the start of COHS (i.e. control the timing)

oral contraceptives

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

oral contraceptives: control the ________ of menses and the _______ of COHS (i.e. control the __________)

onset, start, timing

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

oral contraceptives: control the onset of ________ and the start of ________ (i.e. control the timing)

menses, COHS

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

____________: prevent premature LH surge or disruption of COHS (decrease natural LH surge for timing purposes)

GnRH antagonists/agonists

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

GnRH agonists/antagonists: prevent premature _______ _______ or disruption of COHS (decrease natural _______ _______ for timing purposes)

LH surge

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

_____________: stimulate development of multiple ovarian follicles for oocyte retrieval

gonadotropins (FSH or FHS+LH)

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

gonadotropins: stimulate development of multiple ovarian _________ for oocyte retrieval

follicles

role of meds in Controlled OHS in IVF cycle

stage 1: controlled ovarian hyperstimulation

gonadotropins: stimulate development of multiple ovarian follicles for _______ _________

oocyte retrieval

role of meds in Controlled OHS in IVF cycle

stage 2: oocyte retrieval

_________: induces final follicular maturation for oocyte retrieval (i.e. creates an “artificial” and perfectly timed LH surge)

hCG (or GnRH agonists)

role of meds in Controlled OHS in IVF cycle

stage 2: oocyte retrieval

hCG (or GnRH agonists): induces final follicular maturation for oocyte retrieval (i.e. creates an “artificial” and perfectly timed ________)

LH surge

role of meds in Controlled OHS in IVF cycle

stage 3: luteal phase support

__________: maintains endometrium for embryo transfer and implantation

progesterone

role of meds in Controlled OHS in IVF cycle

stage 3: luteal phase support

progesterone: maintains _________ for embryo transfer and implantation

endometrium

infertility is defined as _________ of unprotected intercourse OR _________ of unprotected intercourse if >35 y/o

12 months, 6 months

infertility is defined as 12 months of unprotected intercourse OR 6 months of unprotected intercourse if >____ y/o

35

the causes o infertility are evenly split between men, women, and unknown/both

there is greater efficacy for treatment of _________-focused treatments

female

___________ is most common cause of anovulatory infertility and is caused by a dysregulation in gonadotropin release, androgen excess, and insulin resistance

PMOS

PMOS is most common cause of _________ infertility and is caused by a dysregulation in gonadotropin release, androgen excess, and insulin resistance

anovulatory

PMOS is most common cause of anovulatory infertility and is caused by a dysregulation in ___________ release, _______ excess, and insulin resistance

gonadotropin, androgen

oral options for fertility treatment include __________ (specifically for PMOS), SERMs and aromatase inhibitors

Metformin