Infertility and Female Infertility

Infertility Definition

Infertility is defined as the inability of a couple to conceive after one year of unprotected intercourse. Investigations should begin after this period. However, if the female partner is 35 years or older, investigations should start after six months. If the female is 40 years or older, begin investigations after three months. The term "infertility" is sometimes replaced by "subfertility" due to psychological considerations.

Contribution to Infertility

Both partners contribute to infertility:

• Female partner: 40-55% of cases

• Male partner: 20-40% of cases

• Unexplained infertility: 10% of cases

In some couples, both male and female factors may be responsible, exceeding 100% when added.

Basic Infertility Investigations

The three basic investigations for infertility are:

1. Semen analysis

2. Tests for ovulation

3. Tests for tubal potency (HSG - Hysterosalpingography)

General Terms

• Fecundability: The probability of achieving pregnancy in one cycle; approximately 20% in the first cycle after marriage.

• Fecundity: The probability of achieving a live birth in one cycle; approximately 15-20% in the first cycle after marriage.

• Primary Infertility: The couple has no history of past pregnancy.

• Secondary Infertility: The female has a history of past pregnancy, regardless of the outcome (including abortions).

Causes of Female Infertility

Common causes of female infertility include:

• Ovarian causes

• Tubal factor infertility

• Uterine causes

• Cervical causes

• Unexplained infertility

Ovarian Causes & WHO Classification

Ovarian causes are classified according to the WHO classification:

• Class 1: Hypogonadotropic Hypogonadism: Decreased FSH and estrogen levels, leading to anovulation. The cause is typically in the hypothalamus or pituitary (e.g., Kallmann syndrome).

• Class 2: Normogonadotropic Normogonadism: Normal FSH and estrogen levels. Seen in PCOS (Polycystic Ovary Syndrome) patients. This is the most common cause of anovulation and the most common ovarian cause of infertility.

• Class 3: Hypergonadotropic Hypogonadism: Increased FSH and decreased estrogen levels due to the lack of negative feedback from estrogen, often seen in ovarian failure (premature menopause or Primary Ovarian Insufficiency - POI).

Important Note: In Classes 1, 2, and 3, prolactin levels should be normal. Increased prolactin causing anovulation is a separate category.

Increased Prolactin

Increased prolactin leads to a negative feedback on GnRH, resulting in decreased LH and FSH and subsequent anovulation. This is typically categorized separately from WHO classes 1-3, though some textbooks may list it as Class 4.

Class 2 Anovulation (PCOS)

Class 2 anovulation (PCOS) is the most common and easily treatable cause of anovulation and ovarian-related infertility.

Tests for Ovulation

Tests for ovulation can be divided into two categories:

1. Tests that predict the time of ovulation.

2. Tests that confirm ovulation has occurred.

Tests confirming ovulation rely on progesterone levels, which are maximal eight days post-ovulation (day 22 of a 28-day cycle or one week before menstruation in irregular cycles).

Predicting Ovulation

• Urine LH Kits: These kits detect the urinary LH surge, indicating that ovulation will occur after 24 hours. In serum, ovulation happens 32-36 hours after the LH surge. These kits detect the LH surge but do not guarantee ovulation. They are less reliable in PCOS patients due to already elevated LH levels.

• Follicular Monitoring (Transvaginal Ultrasound): TVS is performed from day 10 of the cycle onward to study follicle size. Follicle size increases by approximately 2 mm per day. Signs of ovulation include a follicle reaching 18-20 mm, sudden decrease in follicle size giving a crumpled appearance, fluid in the Pouch of Douglas, and a triple-layered appearance of the endometrium. When a follicle reaches 18-20mm an injection of hCG is given to trigger ovulation.

Signs of Ovulation on Ultrasound

• The Trilaminar appearance of the endometrium in late proliferative phase or at the time of ovulation.

• In early proliferative phase, a single echogenic line of the endometrium.

• In the secretory phase, a thick echogenic endometrium with posterior acoustic enhancement.

Predicting Ovulation Time (hCG Injection)

When the follicle reaches 18-20 mm, hCG injection is given to induce ovulation, mimicking the LH surge. Intercourse should occur 32-36 hours post-hCG injection. Signs of ovulation are then monitored.

Endometrial Appearance on Ultrasound

• Early Proliferative Phase: Thin endometrium with a single echogenic line.

• Late Proliferative Phase: Triple-layer (trilaminar) appearance.

• Secretory Phase: Thick, echogenic endometrium with posterior acoustic enhancement (due to glandular secretions).

Posterior acoustic enhancement is a better marker of the secretory phase than endometrial thickness.

Tests Confirming Ovulation

These tests are based on progesterone presence or progesterone-induced changes on day 22 of the cycle:

• Vaginal Epithelium Study: Under estrogen's influence, superficial cells are predominant; under progesterone, intermediate cells prevail. Ovulation is indicated by intermediate cell predominance.

• Cervical Mucus Study: Estrogen leads to thin, watery, abundant mucus with ferning. Progesterone results in thick, non-elastic, viscous, and scanty mucus without ferning. Absence of ferning on day 22 indicates ovulation.

• Basal Body Temperature (BBT) Test: BBT is taken orally before getting out of bed. A mid-cycle increase of 0.4-0.8°C or 0.5°F indicates ovulation.

• Serum Progesterone Levels: Levels $\geq$ 3 ng/mL on day 22 indicate ovulation. This is the best and most reliable test to confirm ovulation.

• Endometrial Biopsy: Though reliable and still relevant in countries such as India to rule out genital TB, this invasive method is becoming less common in developed countries. TB is an indication of endo biopsy in India. Endometrial biopsy is performed in the premenstrual phase (2-4 days before menstruation) to detect genital TB with secreted tubercals. Secretory endometrium indicates ovulation, proliferative endometrium indicates no ovulation. A lag of $\geq$ 2 days between endometrial dating and the patient's reported cycle day suggests luteal phase defect (decreased progesterone). It is also useful for atypical uterine bleeding to rule out endometrial hyperplasia and endometrial cancer.

Management of Anovulation

• For anovulation due to PCOS, the drug of choice is letrozole, starting at 2.5 mg from days 3-7 of the cycle, increasing to 5mg if needed.

• For other causes of anovulation, clomiphene citrate is preferred, starting at 50 mg from days 3-7, increasing up to 150mg if needed.

Follicular monitoring is essential with both letrozole and clomiphene, with hCG given to trigger ovulation when follicles reach 18-20 mm.

Adjuvant Therapy for Anovulation

• Prednisolone may be added if androgen levels are high.

• Metformin may be used if insulin resistance is present.

Clomiphene or letrozole are given for three cycles. If ovulation does not occur, HMG (Human Menopausal Gonadotropin) is considered. HMG is commonly used for IVF, in cases where clomiphene and letrozole fail, and in hypogonadotropic hypogonadism.

HMG (Human Menopausal Gonadotropin)

*HMG is the most common ovulation induction drug for IVF.
*HMG is indicated if clomiphene and letrozole fail,
*In hypogonadotropic hypogonadism.
*In unexplained infertility after clomiphene fails.

For Clomiphene, and Letrozole you need an intact hypothalamic, pituitary, ovarian axis.

HMG carries a high risk of Ovarian Hyperstimulation Syndrome (OHSS), requiring careful monitoring of estradiol levels and follicle size. If $Estadiol \geq 2500 picograms$, withhold hCG to prevent OHSS. Monitor by serial measurements of estradiol and TVS to monitor the size and the number of follicles.

Detecting Ovulation Test

• The best test to detect ovulation is hormonal study.

• The most commonly done test is TVS or follicular monitoring.

Class 1 & 3 WHO

• In Class 1 (Kallmann syndrome), management involves pulsatile GnRH.

• In Class 3 (hypergonadotropic hypogonadism), consider tests for ovarian reserve to check for the presence of follicles in the ovary.

Tests for Ovarian Reserve

*Test the sufficient amount of follicles present in the ovary or not. It is not a basic investigation. *Indications: Age $\geq$ 35 years old, chronic smoker, family history of premature menopause, history of surgery, radiotherapy or chemotherapy, and unexplained infertility.

Clomiphene Citrate Challenge Test

• Measure baseline FSH on day 3. Give clomiphene from days 5-9.

• Measure FSH again on day 10.

• High FSH levels on day 10 indicate poor ovarian reserve as increased FSH wont be able to sufficiently stimulate the follicles and produce estrogen needed to bring FSH back down.

Decreased Ovarian Reserve Management

Management involves donor egg plus IVF, as the number of follicles cannot be increased.

Tubal Factor Infertility

Often results from infections, inflammation. Tubal patency is tested using HSG (Hysterosalpingography.) These are the causes that lead to infertility: PID, salpingitis, endometriosis.

Hysterosalpingography (HSG)

HSG is the investigation of choice whenever you have to test the patency of the tubes. It is an OPD procedure, no anesthesia needed. The analgesic is given half an hour before. A radio-opaque dye (urografin - iodine-based, water-soluble) is passed through a Leech Wilkinson cannula (HSG cannula). Serial X-rays are taken to assess dye passage.

Findings on HSG

• Normal tubes appear narrow and coiled.

• There should be B/L spillage of dye from the fimbrial end.

• Do not see Mullerian anomalies (but could show up by coincidentally). The tubes are never rigid. They're never pipe like.

Ideal Time for HSG

The Ideal time for HSG testing is in pre-ovulatory phase (days 6-11) to avoid interrupting a pregnancy. The ideal time is Day 10.

Contraindications for HSG

The Contraindications for HSG include pregnancy, PID(Pelvic Inflammatory Disease) and genital TB (spread of infection).

Drawbacks of HSG

• Cannot view the exterior of the tube.

• Cannot clearly see/assess the uterine contour (not ideal for Mullerian malformations).

• Pain can induce cornual spasm, causing false bilateral blockage.

  • Physiological is the most common reason that creates bilateral block appearance of HSG

Pathology seen with HSG

*On HSG, I can see that blockages: It could be proximal, could be mid segmental or the distil.
*Distal Block causes dye to collect behind the block, leading to a dilation of the tube: Hydroalpinx. This means there is a distal block.

Müllerian Malformations

Although an accidental finding, HSG is not the investigation of choice for Mullerian Malformation (3D ultrasound is the best, MRI is the gold standard.

Filling Defects

Three main conditions:

1. Submucous fibroid.

2. Polyps

3. Asherman Syndrome

   *Polyp Fibroid Both are smooth, regular filling defect.
   *Asherman Syndrome is multiple, irregular filling defects. (Moth-eaten appearance).

Salpingitis

Honeycomb appearance on HSG is seen in salpingitis isthmica nodosa: In HSG, you never never say it is TB

Genital Tuberculosis Appearances

For Genital TB, HSG can also show : Lead Pipe Appearance, Bearded Appearance, Tobacco pouch like appearance, Golf stick appearance, Cotton wool appearance, all these in the tubes. Normal Tubes: Are narrow, coiled, never rigid/pipe-like.

HSG Scenarios

In Image A : Showing everywhere has dye inside cervix, but there places the dye is not, called Filling defect.

With A : You have single filling defect SMOOTH REGULAR: (POLY FIBROID): Base on HSG can't distinguish, ask which has broad base or suggest with fibroid.

Multiple Multiple multiple multiple multiple multiple, Saw multiple show : Multiple irregular filling defect: Ashernman Syndrome

Laparoscopic Chromopertibation

HSG is not gold standard, Gold standard is Laparoscopic Chromopertibation : per vagina
putting cannula , blue. The advantage of laparoscopic chromoportibation is that
patient is going to be under general anesthesia and patient is going to be fully relaxed
Advantage of Laparoscopic: Also look at spillage of dye, exterior of tubes as well. HSG CANNOT SEE THE TUBE, exterior..

Blue dye = tubes is patent

Management in Laparoscopic

You Treat with the bilateral blockage

In the IS HSG image: the die went to cervic, uterus from uterus can into see tube: Bilateral colonial block: if ask the most common most cause is Physiological. If they ask, what is most common Pathological =Genital TB

What is next step after diagnosis: Go to hysteroscopy: Pass a guidewire from uterus for Fallopian and it does spams relief! You are going see if it clears, You were relieved. This is called hysteria scopic cannulation. Do pregnancy cycle highest conceiving now If can go to IVF. A UNILATERAL block is always going come clomiphene citrate plus IUI.

Always give Clomiphene for controlled ovarian stimulation. Always for unilateral blocks you can clomiphene plus IUI, bilateral just depend the site of the bilateral blocks. Proxima, distal
If have HSG and show abnormal has bilateral and show has Proxmital Cornal: Hystoscopy / Laparoscopy: name complete: hysteroscopic cannulation, laparoscopic chromopertubation. Hystero and laparo: pelvic Scopy.
HSG, you are getting bilateral DISTIL block the next is just simply Laparoscopy. (chromopertibation gold stand.

The distal you know you doing laparoscopy number one to gold stain confirmed! 2 Asses the the severity of the problem at same time can do treatment. Distal which is mild going to do fimbrioplasty and you create a new opening which we call neoalpingostomy.
Distal Block is Mild. But if age is Greater then female: decrease reserve, (IVF)
In bilateral severe distal tube is just do IVF.

Hydrosalpinx shows indicate severe diseases. Indicate worst reproductive or come. Conventional does removal tubes bilateral salpingectomy the hydrosalpinx cannot uterus the in present fluid so either applied the on present fluid clips end proximal.
Always when hydrosalpinx next become LAPAROSCOPIC chormopertibation at it make you sure that it for: is 50 management become you get hydrosalpinx 51 HS Management one end, bilateral and IVF and.

HSG : MID SEGMENTAL? : means undergoing TUBAL sterilization site common tube is ISTHMUS.
Reversal depends if: Age is Less then 35; clip fallop you had for sterilization; isthmus isthmus: Total tube is > 4cm.
Time it takes is never. If not you is not going show it there in for it the asking is it the fact asked tubial is and is 5th 4th tube for except tubal between that performed reversal asked 60 the length point not that 61 to.

Uterine factor inferility: All submous fibroid cause problem. All fibroid that distractal all that >5cm/ fibroid. So fibriod that are not associate problem. Polp yes. Asherman also lead problem. Cromic endromitrious; dietily stilbystrol problem. Gold Hylerscopy (polp and sine) All interautinal, hysteroscopy is your friend

Uterine Malformation is more current pregnancy (septical uterus)

Cervical Steniosis, cervical infections and antisprem Antibotics lead lead factor inferality: You skip the cercix from here.

Sime hurnar test, antisprem is roting spermicide aorun it.

Immunnologlical lead spermicides antibodies:

IUI with cilmphin lead it. 54 that for in and cycle three lead for with IVF. that 333 The with citrate 33 fourth clomiphene 34 and The

In end you you in the video clip where at end