Female infertility

Question 1

General findings

Answer 1

-Infertility is defined as the inability of a couple to conceive despite one year of unprotected sex

💥 Anovulation and impaired fallopian tube motility are the prevalent causes

• Hormone tests for assessment of ovulatory function, and evaluation of tubal patency.
• Treatment focuses on the underlying cause of infertility, e.g., sex hormone substitution and administration of clomiphene citrate or gonadotropins to stimulate ovulation. Surgery is indicated if structural issues e.g., tubal adhesions are present. In vitro fertilization is used for causes of both male and female infertility.

Question 2

Definition

Answer 2

Infertility: inability of a couple to conceive despite 1 year of unprotected sex

1. Primary infertility: infertility in women who have never been pregnant or in men who have never successfully conceived with a partner
2. Secondary infertility: infertility in women who have previously conceived; infertility in men who have previously induced pregnancy
3. Recurrent pregnancy loss: inability of a woman to carry to live birth even if conception is possible (e.g., caused by uterine myomas, antiphospholipid syndrome 👓)

Question 3

Epidemiology

Answer 3

🧨Infertility affects approx. 10–15% of couples of reproductive age.

Approx. 5% of women in the US aged 15–44 years old are infertile.

Question 4

Eziologia

Answer 4

Both sexes

-Systematic and endocrine diseases: diabetes mellitus, hypertension, thyroid disorders, obesity, Cushing’s syndrome, celiac disease, chronic diseases (e.g., hepatic or renal) (Liver cirrhosis, for example, causes hyperestrogenism and can reduce fertility in men.)

-Infections (e.g., chronic chlamydia infection, PID)
Various prescription drugs, alcohol, nicotine, recreational drugs

Female infertility

✔Ovarian insufficiency (30%)
✔Impaired ovum transport in fallopian tubes (30%): fallopian tube adhesions and/or obstruction

-Sexual dysfunctions (10%): sexual arousal disorder, genito-pelvic pain disorder (pain and vaginal tightening during intercourse)

-Diminished ovarian reserve (10%)
Most commonly normal part of aging, but can also be caused by underlying disorder.Decline in functioning oocytes (either reduced number or impaired development)

• Uterine causes (5%) :
  1. Anatomical anomalies (see anomalies of the female genital tract)
  2. Uterine leiomyoma
  3. Asherman’s syndrome: mostly iatrogenic scarring, fibrosis, and/or adhesions of the endometrium caused by curettage (in caso di aborto spontaneo incompleto); 4.Reduced sensitivity of the endometrium to progestogens
• Cervical anomalies (5%)
• Antisperm antibodies in the cervical mucus
• Hypogonadotropic hypogonadism
• Functional hypothalamic amenorrhea
• PCOS 🧨
• Hyperprolactinemia (e.g., pituitary adenoma)(tra le principali cause di amenorrea)

Question 5

Clinica

Answer 5

-Symptoms of anovulation: amenorrhea, irregular menses

Question 6

Diagnosi

Answer 6

A.History of both partners , especially gynecological history

B.Assess ovulatory function (ricorda che l’insufficienza ovarica da sola causa il 30 % dei casi di infertilità nella donna) :

1. Body temperature analysis to monitor menstrual cycle (The basal temperature curve should have a biphasic course, with an increase in body temperature of approx. 0.5° C during the second half of the cycle. Deviations from this pattern indicate menstrual cycle abnormalities.)
2. Hormone tests (between the 3rd and 5th day of the menstrual cycle ) (Hormone levels vary the least during this period in the cycle. Irregular hormone levels in this phase suggest a disorder in follicular maturation, which can be the cause of infertility.)

• Mid-luteal serum progesterone level: progesterone should increase shortly after ovulation → failure of progesterone levels to rise indicates anovulation
• Prolactin and androgen levels: elevated levels induce negative feedback to the hypothalamus → inhibits GnRH secretion → lowers estrogen levels and suppresses ovulation
• FSH levels: elevated in ovarian insufficiency and indicate reduced ovarian reserve
• TSH levels: elevated levels in hypothyroidism
• Prolactin levels: hyperprolactinemia

3.Endometrial biopsy: usually performed 1–3 days before menstruation to determine thickness of endometrium → flat endometrial lining indicates a defect in the luteal phase of the menstrual cycle

C.Assess patency of fallopian tubes and uterus:

1.hysterosalpingography (A radiologic procedure in which contrast dye is injected into the cervical canal and serial x-rays are obtained in order to evaluate the uterine cavity and morphology/patency of the fallopian tubes) or sonohysterosalpingography (A ultrasound technique in which fluid is inserted into the uterus via the cervix to examine the uterine lining.)
-Indications: If the initial work-up does not reveal any
abnormalities and no history suggestive of tubal
obstruction
-Screen for tubal occlusion and structural uterine
abnormalities (e.g., septate uterus, submucous
fibroids, intrauterine adhesions)
-Can also be therapeutic since it removes small
adhesions or mucous plugs obstructing the tubal
lumen
-If evidence of intrauterine abnormalities or tubal
occlusion → hysteroscopy and/or laparoscopy
indicated

D.Examine cervix: Pap smear and physical exam; testing for antisperm antibodies in cervical mucus

Question 7

Treatment

Answer 7

1. Ovulation induction
   - Clomiphene citrate (Inhibits hypothalamic estrogen receptors and thereby the negative feedback of estrogen to the hypothalamus that normally leads to decreased secretion of gonadotropins)
   - GnRH (pulsatile): stimulates the release of FSH, LH → follicle maturation

-Gonadotropins (e.g., recombinant hCG, recombinant LH): stimulate final oocyte maturation → ovulation
Tamoxifen (selective estrogen receptor modulator)

• GnRH-antagonists, da utilizzare in fase follicolare! (GnRH receptor antagonists (e.g., ganirelix) bind to the pituitary GnRH receptors and decrease the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). The decrease in LH and FSH subsequently leads to decreased production of androgens and estrogen. If administered in the late follicular phase, it can prevent premature ovulation.)
• Oocyte donation
• Surgical removal of tubal, cervical, or uterine adhesions, as well as myomas and scar tissue

-(da due fino ad un massimo di 5 embrioni) Assisted reproductive technology :
1.In vitro fertilization (most common) : Hormonal
follicular stimulation → transvaginal follicular puncture
for oocyte retrieval with ultrasound monitoring →
recovered oocytes are mixed with processed
spermatozoa; incubation → intrauterine transfer of
two (in young women) to a maximum of five (in
women over 40) embryos in the cleavage or
blastocyte stage

2.Intracytoplasmic sperm injection

💥Treatment of underlying causes: e.g., levothyroxine, bromocriptine (for hyperprolactinemia), metformin (for PCOS)