Female Reproductive Disorders and Drug Therapies

What is the fertility rate in the US as of 2025?

1.6 children per women

What are the causes of the low fertility rate?

Mulifactorial: economic stability, geopolitical concerns, environmental, etc.

Infertility affects __ in __ couples

1 in 8

What is the definition of infertility?

The inability to achieve a pregnancy over 12 months of unprotected intercourse

When is it recommended to initiate evaluation for infertility for someone over 35 years of age?

After 6 months of attempting prenancy

When is it recommended to initiate evaluation for infertility for someone over 40 years of age?

Immediately

What are 4 causes of female infertility?

1. Ovulatory disorders

2. Tubal infertility

3. Uterine and cervical issues

4. Endometriosis

What are 4 ovulatory disorders that might cause infertility?

1. PMOS

2. Hyperprolactinemia

3. Hypothalamic dysfunction

4. Ovarian insufficiency

What are 3 tubal infertility causes?

1. Pelvic inflammatory disease (PID)

2. STDs

3. Previous complications (ectopic pregnancy, surgery)

What are 3 uterine and cervical issues that might cause infertility?

1. Uterine fibroids

2. Endometrial polyps and adhesions

3. Cervical stenosis

What does PMOS stand for?

Polyendocrine Metabolic Ovarian Syndrome

PMOS used to be called...

Polycystic Ovarian Syndrome (PCOS)

Why was PCOS renamed to PMOS?

PCOS implied the presence of pathological cysts in the ovary, which are sometimes just follicles with interrupted maturations which are not the cause or fundamental characteristics of the disease. It is a multisystemic disorder, not just reproductive disorder.

The Polyendocrine Metabolic part of PMOS refers to...

- Insulin resistance

- High visceral adiposity

- Hormonal disruption

The Ovarian Syndrome part of PMOS refers to...

problems with ovulation and multiple possible comorbidities including DM2, CV, OSA, depression, etc.

__ in __ teen girls and young women are at risk for PMOS

1 in 4

PMOS affects ____% of women

5-18%

What is the leading cause of anovulatory infertility?

PMOS

What are 4 key symptoms of PMOS?

- hyperandrogenism (hirsutism, acne, alopecia, oily skin)

- ovulatory dysfunction (irregular periods)

- polycystic ovaries

- insulin resistance (obesity, metabolic syndrome, skin tags)

- acanthosis nigricans

What are 4 risk factors for PMOS?

1. Genetics

2. Insulin resistance and type 2 diabetes

3. Obesity

4. Environmental pollutants

What are 7 complications of PMOS?

1. Infertility

2. Type 2 DM

3. Gestational diabetes

4. Metabolic syndrome

5. Sleep apnea

6. Endometrial cancer

7. Miscarriage or preterm birth

What are 4 pathophysiologic reasons of PMOS?

1. Genetic and environmental factors that predispose to insulin resistance and hormonal imbalance

2. Insulin resistance and hyperinsulinemia leads to increase ovarian androgen production

3. Excess androgens disrupt follicle development and leads to multiple immature follicles (cysts)

4. Low/imbalanced FSH and high LH can lead to poor ovulation

What labs/tests can be done to test for PMOS?

1. A1c, blood glucose

2. Weight and waist circumference

3. Total/free testosterone, FSH, LH, estradiol levels

4. Cycle tracking

5. Ultrasound

6. Transvaginal ultrasound

What makes up the Rotterdam Criteria of PMOS?

1. Hyperandrogenism

2. Ovulatory dysfunction

3. Polycystic ovaries on ultrasound

What clinical signs or lab evidence indicates hyperandrogenism?

Clinical: hirsutism, acne, alopecia

Labs: Increased testosterone, DHEA, and androstenedione

Ovulatory dysfunction is defined as...

Oligomenorrhea (cycles >35 days apart) or amenorrhea (>3 months without a cycle)

What are "polycystic" ovaries?

≥20 follicles in one ovary or large ovarian volume

There are __ phenotypes of PMOS

7

List 5 general treatment approaches for PMOS

1. Lifestyle modifications (wt loss and exercise)

2. Treat T2DM if impaired glucose tolerance (metformin)

3. Statins if lipids/BMI is not ideal

4. Symptom-based treatment for hirsutism, alopecia, acne

5. GLP-1 agonists (individualized)

How are menstrual irregularities treated in PMOS?

- Hormonal contraceptives or hormonal IUD (Depo-Provera, Yaz, Yasmin 28)

- Provera 10 mg x10d (to restore menstrual cycle)

- Metformin (2nd line, 1,500-2,000 mg/d)

What androgen lowering therapies are used to treat PMOS?

- Spironolactone 25-100 mg BID

- Finasteride 1 mg

What is an important consideration when prescribing Finasteride for PMOS androgen lowering?

teratogenicity

What drugs are used to treat infertility (ovulation induction) in PMOS?

- Letrozole 2.5 mg x5d (better evidence)

- Clomiphene

Endometriosis is a chronic condition in ___% of women

10%

Endometriosis is the cause of __% of infertility cases

38%

What is endometriosis?

When endometrial-like tissues grows outside of the uterus

What are some symptoms of endometriosis?

- Chronic pelvic pain

- Dysmenorrhea

- Infertility

- Dyspareunia

- Dysuria

- Dyschezia

- Chronic fatigue

What are some risk factors for endometriosis?

- Genetics

- Immune system dysfunction

- Short menstrual cycles

- Heavy prolonged period

- Environmental factors

What are some complications of endometriosis?

- Infertility

- Chronic pelvic pain

- Adhesions and scar tissue (outside of reproductive organs like bladder and bowel)

- Bowel and bladder issues

- Cancer risks

Where is endometrial tissue most commonly found outside the uterus in endometriosis?

Ovaries, fallopian tubes, pelvic peritoneum

What is the pathophysiology of endometriosis?

Retrograde menstruation - menstrual blood flows backward through the fallopian tubes into pelvic cavity containing endometrial cells. This leads to endometrial-like tissue growing outside the uterus, inflammation, development of fibrosis and adhesions, and hormonal dysregulation

Why is hormonal dysregulation a symptoms of endometriosis?

Ectopic tissue stimulates release of estrogen, leading to more endometrial growth

What methods are used to diagnose endometriosis?

- Confirmed by histopathological examination of removed lesions

- Ultrasound

- MRI

- CT scan

- Laproscopy

What are the goals of therapy for endometriosis?

- Pain management

- Improving QoL

- Restoration of fertility (if desired)

Which drugs are used for endometriosis pain mangement?

NSAIDs (ibuprofen, naproxen, diclofenac)

What are the 1st line pillars of endometriosis treatment?

1. NSAIDs

2. Combined hormonal Contraception

3. Progestins

What are 2 second line options for endometriosis treatment?

GnRH agonists and GnRH antagonists

What are 4 examples of GnRH agonists used to treat endometriosis?

- Goserelin 3.6 mg monthly subQ

- Leuprolide 3.75 mg IM monthly

- Nafarelin 400 mcg intranasally daily-one spray AM, one spray PM

- Triptorelin 3.75 mg IM monthly

What are 2 examples of GnRH antagonists used to treat endometriosis?

- Orilissa 150 mg daily or 200 mg BID

- Myfembree (relugolix/estradiol/norethindrone) daily

What is a last line treatment option for endometriosis?

Aromatase inhibitors like anastrozole, letrozole, danazol (synthetic androgen)

What are the 6 stages of IVF?

1. Consultation and testing

2. Ovarian stimulation

3. Egg retrieval

4. Fertilization

5. Embryo transfer

6. Pregnancy test

What does ART stand for?

Assisted Reproductive Technology

What are some advantages of IVF?

- Effective

- Genetic screening possible

- Option for fertility preservation

- Donor gametes possible

- Surrogacy possible

What are some disadvantages of IVF?

- COST

- Multiple pregnancy risk

- Ovarian hyperstimulation syndrome

- Invasive procedures

- Emotional and psychological stress

- Ethical concerns

What do you need medications for in IVF?

- Stimulate ovaries to produce eggs

- Help eggs mature into follicles

- Prevent early ovulation

- Prepare the uterine lining

Which medications are used to control the cycle and suppress the ovariaries?

Birth control

Which medications are used to stimulate the ovaries?

- FSH analogs like follitropin alfa, follitropin beta, cortifollitropin alfa, urofollitropin

- FSH + LH menotropins (Menopur, Reproex)

- Clomid to grow follicles (fewer injections)

What medications are used to prevent premature ovulation? Day 5-6 onward

- GnRH agonists like Lupron, Synarel, Suprecur, Zoladex

- GnRH antagonists like Ganirelix, Cetrotide

What medications are used to trigger ovulation to retrieve mature eggs?

- Human chorionic gonadotropin hCG (Pregnyl, Novarel, Ovidrel)

- Gonadotropin releasing hormone GnRH agonist trigger in antagonist cycle (Leuprolide)

When does egg retrieval occur after medication to trigger ovulation is given?

36 hours

How is the endometrium prepared for egg implantation?

- Lupron injections to control ovulation

- Estradiol to thicken lining

- Progesterone before transfer to make lining habitable

What are some common side effects from IVF medications?

- Soreness/bruising at site of injection

- Nausea/bloating/cramps/abdominal pain

- Breast tenderness

- Increased vaginal dryness

- Mood swings

- Fatigue

- Hot flashes

- Headaches

- Lower back pain

- Weight gain

Describe the process of an embryo transfer

- Outpatient procedure

- Ultrasound guided catheter

- Embryo implants within first few days

- 2-week wait then blood test to confirm pregnancy