Presented by Dr. SuryaModerator: Dr Shailaja

Female Infertility

Definition Epidemiology Risks Ovarian Reserve Tests Etiology Investigations

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Female Infertility

Infertility ◦ 1 year of unprotected intercourse without conception.

Subfertility ◦ not sterile but exhibit decreased reproductive efficiency

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Definition

Female Infertility

Primary infertility- no previous pregnancies

Secondary infertility-a prior pregnancy, although not necessarily a live birth

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Female Infertility

Fecundability __probability that a cycle will result in pregnancy (estimated at 20% to 25%)

Fecundity is the probability that a cycle will result in a live birth.

On the basis of this estimate, about 90% of couples should conceive after 12 months of unprotected intercourse

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Female Infertility

Affects 10-15% of reproductive age couple

Reproductive efficiency averages 20%

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Epidemiology

Female Infertility

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Time required for conception Among couples who will attain pregnancy

Month of exposure % pregnant

3 months 57%

6 months 72%

1 year 85%

2 years 93%

Female Infertility

The human reproductive process is complex, but for purposes of evaluation, it can be dissected into its most important and basic components.

Sperm must be deposited at or near the cervix at or near the time of ovulation, ascend into the fallopian tubes, and have the capacity to fertilize the oocyte (male factor).

Ovulation of a mature oocyte must occur, ideally on a regular and predictable basis (ovarian factor).

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Female Infertility

The cervix must capture, filter, nurture, and release sperm into the uterus and fallopian tubes (cervical factor).

The uterus must be receptive to embryo implantation and capable of supporting subsequent normal growth and development (uterine factor).

The fallopian tubes must capture ovulated ova and effectively transport sperm and embryos (tubal factor).

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Female Infertility

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Causes of infertility %

Male factor 25-40%

Female factor 40-55%

Both male & female 10%

Unexplained infertility 10%

Male problems; Sales; 35; 35%

Tubal and pelvic pathology; Sales; 35;

35%

Ovulatory disfunc-tion; Sales; 15;

15%

Unexplained,10

Unusual problems; Sales; 5; 5%

Female Infertility

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Prevalence of causes of infertility in female %

Ovulatory dysfunction 30-40%

Tubal & peritoneal factor 30-40%

Unexplained infertility 10-15%

Miscellaneous causes 10-15%

Tubal and Pelvic

Pathology; Column1; 40;

40%

Ovulatory dysfunction; Column1; 40;

40%

Unexplained; Column1; 10;

10%

Unusual problems; Column1; 10; 10%

Female Infertility

Age Stress Poor diet Smoking Alcohol STDs Overweight Underweight Caffeine intake Too much exercise

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What Increases the Risks?

Female Infertility

Majority of spontaneous conception ____ within 6 months

Conception rate depends upon the age

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Age Conception rate

≤ 25 years 73%

26-30years 74%

31-35years 62%

> 35years 27% & lower

Age Conception rate

<25 yrs 73%

26 to 30 74%

31 to 35 62%

>35 27%

Female Infertility

Likelihood of success declines by ◦5% for each additional year of the female◦15-25% for each added year of infertility

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Fertility rate Age

Peaks 20-24yrs

↓ 4-8% 25-29yrs

15-19% 30-34yrs

26-46% 35-39yrs

95% 40-45yrs

Fertility rate % Age

20-24

4-8 25-29

15-19 30-34

26-46 35-39

95 40-45

Female Infertility

During fetal life, germ cell proliferation

6-7 million oogonia by 16-20wks

Oocyte

1-2 million at birth

about 3,00,000 by onset of puberty

400-500 oocytes ovulate(35-40 yrs) 15

Physiology of reproductive aging, 1,2,3,4,5,6,7

enters 1st meiotic division

mitosis

Female Infertility

At the time of menopause, 1000 follicles remains

Rate of follicular depletion relatively constant, during reproductive years

Accelerates over 10-15 years

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Female Infertility

Progressive follicular depletion

High abnormalities in aging oocyte

High prevalence of spontaneous miscarriage

High prevalence of benign uterine pathology

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Fertility with aging

Female Infertility

naturally starts to decline after late 20's.

After 35 decreases rapidly.

with time, the supply diminishes, the EGG.

The remaining eggs also age along with the rest of the body.

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Female Infertility

Aimed at identifying individuals at risk for a disease, (DOR).

Should have high specificity, Aim to decrease false-positive results, Avoiding aggressive treatment or inappropriate recommendations in women with a normal ovarian reserve.

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Ovarian reserve tests

Female Infertility

Treating women with unrecognized DOR is undesirable

To minimize the risk for a falsepositive result. Justified in,

1. Age over 35.2. Unexplained infertility.3. Family history of early menopause.4. Previous ovarian surgery (ovarian cystectomy or

drilling, unilateral oophorectomy), chemotherapy, or radiation.

5. Smoking.6. Demonstrated poor response to exogenous

gonadotropin stimulation.

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Female Infertility

Basal FSH and Estradiol concentrations Clomiphene Citrate Challenge Test(CCCT) Inhibin B Antimullerian Hormone Antral Follicular Count Ovarian Volume

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Ovarian reserve tests…..

Female Infertility

Rising FSH levels are one of the earliest signs of reproductive aging

The basal FSH concentration : Simplest and still most widely applied measure

Vary significantly across the cycle, Best obtained during the early follicular phase (cycle day 2-4).

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Basal FSH and Estradiol

Female Infertility

Assays (using IRP 78/549), FSH levels greater than 10 IU/L (10-20 IU/L) have high specificity (80-100%;)

Predicts poor response to stimulation

Sensitivity generally low (10-30 %;) and decreases with the threshold value

Although most women who are tested (including those with DOR) will have a normal result, the test is still useful because those with abnormal results are very likely to have DOR.

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Female Infertility

By itself has little value as an ovarian reserve test,

Provide additional information for interpretation of the basal FSH level

Basal FSH is normal

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Serum estradiol

Normal Basa

l FSH

Elevated basal estradi

ol> 60-80 pg

Poor response

to stimulation

ElevatedBasa

l FSH

Elevated basal estradi

ol> 60-80 pg

Very Poor response

to stimulation

Female Infertility

Provocative and more sensitive test Probes the endocrine dynamics of the cycle under both

basal and stimulated conditions, Before (cycle day 3 FSH and estradiol) and after

(cycle day 10 FSH) treatment with clomiphene citrate (100 mg/d, cycle days 5-9)

A frankly elevated cycle day 10 FSH concentration can identify women with DOR who might otherwise go unrecognized if evaluated with basal cycle day 3 FSH and estradiol levels alone.

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Clomiphene Citrate Challenge Test(CCCT)

Day 3 FSH and estradiol

Clomiphene citrate (100

mg/d, cycle days 5-9)

Day 10 FSH

CCCT

Overall, stimulated FSH levels have higher sensitivity but lower specificity than the basal FSH

Female Infertility

In studies evaluating CCCT results, stimulated concentrations of FSH, estradiol, and inhibin B have varied widely, limiting the value of the test.

2006 systematic review of the predictive value of the CCCT over a range of day 10 FSH concentrations (10-22 IU/L) test had ◦47-98%; specificity and 35-93%; sensitivity for

predicting poor response to stimulation, and ◦67-100%; specificity and 13-66%; sensitivity for

predicting treatment failure.

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Female Infertility

Secreted ◦ primarily during the follicular phase ◦ by the granulosa cells of smaller antral follicles, and ◦ might therefore be expected to have some value as an

ovarian reserve test.

However, serum inhibin B concentrations increase in response to exogenous GnRH or FSH stimulation and vary widely across and between menstrual cycles.

Inhibin B is generally not regarded as a reliable measure of ovarian reserve.

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Inhibin B

Female Infertility

low threshold values (40-45 pg/mL) have only◦ 64-90%; specificity and ◦40-80%; sensitivity for predicting poor response

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Female Infertility

Produced by◦ granulosa cells of preantal and small antral follicles, ◦ beginning when primordial follicles start development and

ending when they reach a diameter of 2-6 mm.

Small antral follicles: larger numbers of granulosa cells and a more developed microvasculature: likely source

Levels are gonadotropin-independent and exhibit little variation within and between cycles

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Antimullerian Hormone

Female Infertility

In the general IVF population, low AMH threshold values (0.2-0.7 ng/mL) ◦ 40-97%; sensitivity, ◦ 78-92%; specificity, ◦ 22-88%; PPV and ◦ 97-100%; NPV for predicting poor response to stimulation

(<3 follicles, or <2-4 oocytes), ◦ but have proven neither sensitive nor specific for

predicting pregnancy

Very promising screening test for DOR, More useful in a general IVF population or in women at high risk for DOR than in women at low risk for DOR

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Female Infertility

20-150 growing follicles in the ovaries at any time, although only a few are large enough to be imaged (≥2 mm) by TVS

Follicles of that size have reached a stage of development where they are responsive to FSH, which stimulates and supports more advanced stages of development. 34

Antral Follicle Count

Female Infertility

The antral follicle count (AFC; total number of antral follicles measuring 2-10 mm in both ovaries) thus provides an indirect but useful measure of ovarian reserve

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Histology- proportional

Number of small antral follicles

2-10 mm

The number of primordial follicles

remaining.

Female Infertility

In the general IVF population, including women at low and high risk for DOR, an AFC threshold value of three to four follicles has ◦ High specificity (73-100%;) ◦ For predicting poor response to ovarian stimulation and

failure to conceive (64-100%;)

A low AFC has high specificity for predicting poor response to ovarian stimulation and treatment failure, making it a useful test, but low sensitivity limits its overall clinical utility.

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Female Infertility

Decreases with follicular depletion. High inter-cycle and inter-observer

variability, ovarian pathology such as endometriomas

and polycystic ovary syndrome, results have limited generalizability.

Ovarian volume (length × width × depth × 0.52) generally correlates with the number of oocytes retrieved, but poorly with pregnancy.

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Ovarian Volume

Female Infertility

A low ovarian volume (< 3mL) ◦ High specificity (80-90%;) and ◦ Widely ranging sensitivity (11-80%;) ◦ For predicting poor response to ovarian stimulation.

◦ The PPV for poor response can be as low as 17%; among women at low risk for DOR, and as high as 53%; in women at high risk.

Overall, ovarian volume has very limited clinical utility as an ovarian reserve test.

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Female Infertility

ANOVULATION AND OLIGOOVULATION

Hypothalamic anovulation◦Psychological factors◦Low BMI and obesity

-disrupts hypothalamic pituitary ovarian axis

- Anorexia nervosa, vigorous athletic training and malnutrition

- Female athlete triad: Secondary amenorrhea eating disorder, osteopenia/osteoporosis

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Ovarian factors

Female Infertility

weight gain ideal treatment

- ↑ caloric intake and weight gain resumption of menses in 90%, sponaneous conception in 73%

- mean weight gain by 3.6kg sufficient for

resumption of ovulationCongenital hypothalamic

failure( Kallmann syndrome)Psychotropic drugsTranquilizers

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Female Infertility

Pituitary ◦Sheehan’s syndrome

- Postpartum pituitary necrosis due to postpartum haemorrhage f/b panhypopituitarisim→ ↓FSH/LH

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Female Infertility

◦Tumor: Prolactinomas- ↑ Prolactin level inhibitory effect on

pulsatile GnRH release→ hypogonadotropic effect

-↓granulosa cell number and FSH binding

-↓granulosa cell estradiol production

-causes inadequate luteinization and reduced secretion of progesterone

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Female Infertility

◦Hypothalamic-pituitary axis dysfunction

Anovulation due to hypogonadotropic-hypogonadism

- Presence of ↓ serum LH, FSH and estradiol

- Causes : Craniopharyngioma Pituitary adenomas Arteriovenous malformation Central space occupying lesion

- Systemic diseases: chronic liver disease, chronic renal failure 43

Female Infertility

Thyroid◦ Prevalence of abnormal TSH in infertility

population

6.3% Anovulatory infertility4.8% Unexplained infertility2.6% Tubal infertility1.55% Male infertility

◦ In one study 23% women with hypothyroidism had irregular menses, likely anovulation

◦ Both hypothyroidism and hyperthyroidism

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Female Infertility

Adrenal: Congenital adrenal hyperplasia Ovarian causes

◦ Polycystic ovarian syndrome

- Most common cause of anovulation and oligovulation in infertility

- ↑LH pulse frequency, ↓FSH

- No folliculogenesis Formation of atretic follicles

- No ovulation cyst formation

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Female Infertility

◦Premature ovarian failure

- Presence of persistently elevated gonadotropins

- Associated with estrogen therapy Activate receptor formation on the follicles

- ↑gonadotropins stimulates follicular growth and development

- Reported with autoimmune disorder

- Demonstration of ovarian autoantibodies

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Female Infertility

◦Luteinized unruptured follicle syndrome

- Ovum trapped inside the follicle gets luteinized

- No ovulation beyond 36hours of LH surge

- Pelvic endometriosis, hyperprolactinomas

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Female Infertility

LUTEAL PHASE DEFECT

- During follicular endometrium exhibit proliferative- During luteal secretory transformation - Inadequate corpus luteum progesterone regarded as cause

of infertility and early pregnancy loss

- ↓progesterone level with luteal phase deficiency

Delayed endometrial maturation

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Female Infertility

Shift in the implantation window

Long delays may threaten embryo viability Prevent implantation

Causes◦ Disturbances in pituitary gonadotropin secretion pattern- ↓GnRH pulse ↓FSH level Ass. With poor luteal function- Rapid GnRH pulse frequency and ↓LH frequency during mid

cycle surge and reduced LH bioactivity

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Female Infertility

◦ Endocrinopathies:◦ affect hypothalamo-pituitary-ovarian axis◦ Hyperthyroidism and hypothyroidism- Changes SHBG level ↑Feedback inhibition in

gonadotropin secretion- Primary hypothyroidism ↑TRH

Stimulates lactotrophs directly activates prolactin gene transcription

Hyperprolactinemia Inhibit GnRH secretion No luteal function ↓Progesterone level

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Female Infertility

◦Other causes

- Endometriosis- Dysfunctional uterine bleeding

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Female Infertility

30-40% of cases of infertility Tubal blockage, peritubal adhesion, fimbrial end blockage Causes :-

◦ Infection - Post abortal, puerperal nfection - STI ( gonococcal , clamydial)

- PID - Tubercular salphingitis

◦ Endometriosis◦ Peritubal adhesions : Previous surgeries

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Tubal factors

Female Infertility

INFECTION

- Polymicrobial in nature, involving both the tubes

- Organisms:- STI: Gonococcus, Chlamydia, Mycoplasma- Pyogenic: Streptococcus, E.coli,Staphylococcus, Gp

B streptococcus, Bacteroide fragilis, actinomycoses- Tubercular: M. tuberculosis

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Female Infertility

Mode of spread: Ascending infection

- Gonococcal infection may affect the tubes during initial exposure or from Bartholin’s gland and cervix

- Pyogenic infection follow: Delivery, induced abortion, minor procedure like D & C, hysterosalphingography, IUCD, infected polyp

- Recently, chlamydia is regarded as common cause, ascends up from the cervix

Direct spread : appendicitis, diverticulitis, pelvic peritonitis

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Female Infertility

Pathogenesis◦ Pyogenic: Infection from uterine cavity & cervix

Pelvic cellulitis Perisalphingitis

Lumen directly infected Endosalphingitis

Produces cornual blockage

◦ Gonococcal: directly ascends to tube through continuity and contiguity

Endosalphingitis

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Female Infertility

Pathology◦ Pyogenic: Outer coat is involved, adhesion are

more and dense

◦ Gonococcal : - Mainly endosalphingitis, adhesions are less and filmsy

- Fimbriae gets phymotic, edematous and indrawn by cicatricle contraction closure of abdominal ostium defective ovum pick up

- Loss of cilia infertility

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Female Infertility

Site of obstruction◦ Proximal : - Prevents sperm to reach distal portion …..hinders

fertilization- Causes: tubal spasm, temporary mucous

plugging,salpingitis isthmica nodosa(23-60%)- Risk of perforation with cannulation ranges from 3%-

11%

◦ Distal: - Prevents ovum capture- Exhibits a spectrum: mild( tubal obstruction),

moderate( fimbrial phimosis) to severe ( complete obstruction)

- Causes: Pelvic infection, Endometriosis, prior abdominal and pelvic surgery

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Female Infertility

Genital tuberculosis ( Tubercular salphingitis)

- Accounts for 5-10% cases of infertility- Infertility , the most common symptom(70-80%)- Secondary to primary infection elsewhere : Lungs (50%), lymph nodes, urinary tract, bones and joints- Fallopian tubes : Invariably the primary site

◦ Mode of spread:- Hematogenous (90%)- Lymphatic - Peritoneum, bowel, mesenteric

nodes- Ascending – Contact with males with

urogenital TB

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Female Infertility

Pathology - Commonest site:Fallopian tube, endometrium- Both tubes involve simultaneously- Initially involve submucosal layer- Spread medially to muscles: Fibrosis- Spread inward to mucosa

- Fimbriae everted ostium is patent- Tubercle burst into lumen pyosalphinx- Spread outside perisalphingitis- Formation of diverticula Salphingitis isthmica

nodosa

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Female Infertility

- 20-40% of infertile women

- Mechanism of infertility: - Distorted adenexal anatomy- Blockage of tubo-ovarian motility due to adhesion- Interference with oocyte development or early

embryogenesis- Reduced endometrial receptibility

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ENDOMETRIOSIS

Female Infertility

- Appendicectomy

- Divurticulectomy

- Surgeries for ectopic pregnancy

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PELVIC SURGERY

Female Infertility

Causes: ◦ Pelvic inflammatory disease◦ Endometriosis◦ Previous surgeries

Distorted anatomy and pelvic adhesion : main mechanism of infertility

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Peritoneal factors

Female Infertility

- Ascending infection and inflammation of the upper genital tract

- Polymicrobial:- STI: N. Gonorrhea 30%

Chlamydia trachomatis 30% Mycoplasma 10%

- Aerobic: E. coli, group B streptococcus, staphylococcus

- Anaerobic: Bacteroids, Peptococcus, peptostreptococcus

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PELVIC INFLAMMATORY DISEASE

Female Infertility

PathologyInitiated in endosalphinx Destruction of epithelial cells, cilia and microvilli

All three layers gets involved Edematous and hyperemic

Exfoliated cells and exudates pour into lumen and agglutinate mucosal fold & plugs

Abdominal ostium closed by indrawing of fimbriae Uterine end closed by congestion

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Female Infertility

Closure of both ostia

Formation of pyosalphix, hydrosalphix

Filmsy adhesions of tube and surrounding structures

Pouring of exudates though the abdominal ostia

Pelvis peritonitis, pelvic abscess, tubo-ovarian abscess

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Female Infertility

Risk of infertility

◦Single episode of PID is significant and increases rapidly with subsequent episodes

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Episode of PID % of infertility

1st 10-12%

2nd 23-35%

3rd 54-75%

Episodes of PID

% of infertility

1st 10 – 122nd 23- 353rd 54- 75

Female Infertility

Mechanism: Defective nidation and implantation

Causes:

CONGENITAL : - Absence of uterus Uterine hypoplasia

CONGENITAL MALFORMATION:- Uterine didelphus(25%), Unicornuate(38%), Septate(25-47%)

- Pregnancy outcome depends upon site of blastocyst implantation

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Uterine Factors

Female Infertility

In utero EXPOSURE TO DIETHYLSTIBESTEROL

- ↑ risk for congenital malformation and obstetric complication

- 70% exposed had uterine malformation

- Most common malformation: T shaped uterus

- Infertility associated with constriction of upper segment of reproductive tract

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Female Infertility

UTERINE LEIOMYOMA

- Various factors affect pregnancy: size, location, number and presence of associated symptoms

Possible mechanism:

- Altered uterine contractility: Disrupt normal sperm migration, embryo transport

- Cornual occlusion by myoma, compression of interstitial segment of the tube

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Female Infertility

Adversely affect vascular and molecular profiles of implantation

Poor regional blood flow

focal endometrial attenuation or ulceration

- A meta-analysis showed:Pregnancy rate increased to 57-67% after abdominal myomectomy for infertiltiy

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Female Infertility

ENDOMETRIAL POLYP

- Incidence of asymptomatic endometrial polyp in infertility ranges: 10-32%

- Overall prevalence after hysteroscopy : 3-5%

- Higher in patients with other symptoms and with endometriosis

- Rare in young women

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Female Infertility

- Menstrual symptoms( hypomenorrhoea, amenorrhoea, dysmenorrhoea) and infertility

Pathophysiology:-- Scant or poorly vascularised and dysfuncitonal

endometrium resulting from- Intraop or postoperative complication- Intrauterine infection

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INTRAUTERINE SYNECHIAE( ASHERMAN’S SYMDROME)

Female Infertility

Intraop and postop complication

- 90% in curattage of pregnancy termination- 22% in postpartum curettage..↑ risk of endometritis- Evacuation of missed abortion, H. mole or after

cesarean section- Abdominal or hysteroscopic myomectomy,

septoplasty, uterine surgery

Intrauterine infection- Genital tuberculosis( tubercular endometritis)- Schistosomiasis

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Female Infertility

CHRONIC ENDOMETRITIS

- Uncommon cause, true prevalence not known- Mucopurulent cervicitis associated with

Chlamydia trachomatis, Mycoplasma genitalis- Significant cause of chronic endometritis with tubal

factor infertility- Chlamydia produces silent tubal infection- Mycoplasma & Ureaplasma recovered from cervix

mucous of infertile couple47% of couple who conceived 53% of couple who remained infertile

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Female Infertility

ANATOMIC- Congenital elongation of cervix- Cervical stenosis( pinhole Cx os)

PHYSIOLOGICAL- Fault in compositon of cervical mucous- Antisperm antibodies

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Cervical factors

Female Infertility

Fault in cervical mucous

- Becomes abundant, clear, watery and easily penetrable by the sperm

- Scant and poorly estrogenised cervical mucous- Cervicitis- Previous injury to cervical glands- Treatment with antiestrogen( Clomiphene

citrate)

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Female Infertility

Anti sperm antibodies

Either autoimmune or allogenic response

Mostly immunoglobulins, Can be free/ agglutinating- IgA: Cervical mucous, seminal plasma- IgG: Cervical mucous, semen- IgM: serum( larger difficult traversing the genital tract)

Causes: - Coital trauma, genital tract infection- Testicular trauma: Torsion - Occlusion of vas deference : Inguinal herniorrhaphy, cystic

fibrosis, Vasectomy reversal

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Female Infertility

Effect- Interference with

- Capacitaton- Acrosomal reaction- Sperm egg recognition & fusion- Cleavage of early embryo

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Female Infertility

Vaginal atresia( partial / complete)

Transverse vaginal septum

Septate vagina Narrow introitus Vaginitis Vaginismus Vulvodynia

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Vaginal factors

Female Infertility

- Is the diagnosis of exclusion, after systematic evaluation fails to identify the cause

- All standard elements of the infertility evaluation yield normal results

- Incidence 10%, as high as 30%

- Avg. fecundity rate in untreated women 2-4%

- Role of diagnostic laparoscopy - 29% of women conceived after 36 weeks of t/t ē laparoscopy

compared to 17%

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Unexplained infertility

Female Infertility

BODY WEIGHT

- Overweight BMI >27, Obese BMI >30

- Underweight BMI < 17

- Disorders of hypothalamic GnRH, Pituitary gonadotroin release

- Mean wt loss of 10.2kg/m2,spontaneous ovulation and pregnancy occurred in 90% and 30% resp

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Life style & Environmental factors

I’m healthy strong person I would not have any problem producing a baby

OBESITY“AN EMERGING MENACE”

1. > 1 Billion overweight

2. > 300 Million – Obese

3. 26% of non pregnant women ages 20 – 39 are overweight / obese

W

H

O

Are obese women at risk of infertility ?

An Obese Woman is about Thrice as likely to be Infertile as

a normal woman

Yes

Obesity and Infertility

Chances of pregnancy is reduced by 5% for every BMI unit that exceeds 29 kg/m2

MOST COMMONLY USED INDEX TO QUANTIFY OBESITY IS BMI

High prevalence of Infertility in Obese women

Obesity can be • Main • Secondary or• Accompanying infertility factor

The impact of obesity on A.R.T. outcomes is debatable

Obesity is strongly associated with

PCOS

CENTRAL PLAYER ………

• Insulin resistance• Hyperandrogenism• Elevated leptin • Leptin resistance

UNDERLYING MECHANISM bothregular or irregular cycle

• anovulation • release of oocytes with reduced

fertilization potential• endometrial abnormalities

“Both seed and soil defective”

British Fertility Society guidelines …

• Infertility treatment should be deferred until BMI<35 kg/m2

• preferably BMI<30 kg/m2 in young women with good ovarian reserve

Treatment ModalitiesFor Infertility in Obesity

Life – Style &NutritionChanges

• Diet• Exercise• Psychological Counseling

Surgical Intervention

• Bariatric surgery

ART

• IUI• IVF• ICSI

Pharmacological interventionAppetite suppressant, Weight Loss Drugs

(Orlistat) Drugs Increase sucidal tendency

Even 5% Weight loss improves fertility outcome

Obese women : not only have a lower chance of pregnancy following In Vitro Fertilization

They require higher doses of gonadotropins and

Have an increased miscarriage rate

OBESITY & ASSISTED REPRODUCTION

obesity and endometriumBellver et al, 2007 2656 first oocyte donation cycles

Lower implantation and pregnancy rates as BMI increases

• Higher miscarriage rate as BMI increases

• Lower ongoing pregnancy rate in OW and OBongoing

PRin BMI<25: 45.5%in BMI>25: 38.3%

Pregnancy after Bariatric Surgery

Pre-Pregnancy Counselling

When ever possible, pregnancy should be

delayed till weight loss stabilizes for 12-24 months.

Weight loss is one of the corner stone to achieve a healthy pregnancy and child birth

Female Infertility

-13% of female infertility relate to smoking

- Higher prevalence of infertility, lower fecundability, longer time of conception

- Mechanism: - Accelerated follicular depletion- Loss of ciliary function- Menstrual cycle abnormalities- Gamete or embryo mutagenesis

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Smoking

Female Infertility

- Marijuana inhibits secretion GnRH - Interferes with ovulatory function- Cocaine impairs spermatogenesis, ↑risk of tubal

disease

ALCOHOL- Heavy alcohol consumption: ↓ fertility- Moderate alcohol consumption: ↓ fecundability- Associated with lower pregnancy rate achieved with

ART

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Substance abuse

Female Infertility

CAFFINE

- Ingestion of >250mg/day : adverse effect- Higher level consumption: Delay conception, ↑

pregnancy loss

ENVIRONMENTAL & INSECTICIDS EXPOSURE- Perchloethylene( dry cleaning), toluene ( printing)- Ethylene oxide- Mixed solvents- Herbicides/ fungicides- Pesticides, chlorinated hydrocarbons

102

Female Infertility

Coital errors◦ Dyspareunia◦ Frequency and timing coitus◦ Use of spermicide

Anxiety / apprehension Family disposition, genetic and constitutional

factors

103

General factors

Female Infertility

Evaluation of infertility focuses on the couple regardless of past reproductive performances

Objective:- To identify and correct specific causes of infertility- To provide accurate information- To provide emotional support- To guide for alternatives ART, use of donar gamete

and adoption- Counseling must be the ongoing process

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Evaluation

Female Infertility

Couple-centered management Access to evidence-based information

(verbal and written) Counseling from someone not directly involved in

management of the couple’s fertility problems Contact with fertility support groups Specialist teams

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Principle

Female Infertility

- All couples who failed to conceive after a year or more of unprotected coitus

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Indication

Female Infertility

- Starts with a careful history and physical examination as ususal

HISTORY- Age , duration of marriage, previous marriage- Occupation - Duration of infertility/ previous evaluation and

treatment- Coital frequency/time of cycle/ sexual dysfunction- Vaginal discharge/ chronic pelvic pain

107

Female infertility evaluation

Female Infertility

MENSTRUAL HISTORY

- Menarche, regularity, characteristics- Mittelschmerz, midcycle spotting, permenstrual

mastalgia - Dysmenorrhoea( onset), dyspareunia- Intermenstrual, post coital bleeding

OBSTETRIC HISTORY- Parity, pregnancy outcomes/losses & complications- Pregnancy termination, septic abortion, ectopic

pregnancy

108

Female Infertility

PAST HISTORY

- Medical illness, previous surgeries, wound infection- H/o thyroid disease, galactorrhoea, headache, visual

field defect, hirsutism- H/o PID , STD- Previous abnormal pap smear, D&C, Cx biopsy, DC

cautery, HSG- H/o tuberculosis, contact history- Drug history, h/o contraception

109

Female Infertility

FAMILY HISTORY- Early menopause, reproductive failure

PERSONAL HISTORY- Use of tobacco, alcohol, smoking, drug abuse- Eating habit, exercise

PHYSICAL EXAMINATION- Weight/ BMI/ Secondary sexual characteristic- Signs of androgen excess- Thyroid enlagement, nodules, tenderness- Breast secretion, character

110

Female Infertility

SYSTEMIC EXAMINATION

- Renal disease, hepatic disease- Abdominal masses, pelvic masses- Vaginal abnormality, cervical abnormality- Abnormal secretions and discharge- Size of the uterus, adenexal masses, tenderness

on cx motion, nodularity in adenexae or cul-de-sac

111

Female Infertility

Initial advice for people concerned about delays in conception:

•Cumulative probability of pregnancy in general population:– 84% in 1st year– 92% in 2nd year

• Fertility declines with a woman’s age

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Female Infertility

• Lifestyle advice:– Sexual intercourse every 2–3 days– ≤ 1–2 units alcohol/week for women; ≤ 3–4 units/week for men– Smoking cessation programme for smokers– Body mass index of 19–29– Information about prescribed, over-the-counter and recreational drugs– Information about occupational hazards

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• Offer preconceptional advice:– Folic acid– Rubella susceptibility and cervical screening

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Any investigation for infertility couple should begin with:- Semen analysis- Confirmation of ovulation- Documentation of tubal pathology

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Investigation

Female Infertility

Initial assesmentTLC/ DC/ Bl group/ RBS/ Hb/ ESR

Chest x ray/sputum AFB/ RFT/ LFT/HVS c/s

Assessment of ovulationFrequency and regularity of mensesEndometrial biopsy (+ AFB culture)

Follicular studyProgesterone level/ FSH,LH level

Urinary LH excretionBBT, Cx mucous study

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Female Infertility

Test for tubal patency

HSG/ Laparoscopy ē chromotubationTVS & Saline hysterosalphingography

(Transvaginal hydrolaparoscopy & fertiloscopy)(Falloposcopy)

Test for uterine abnormalityHysteroscopy

TVS & Saline hysterosalphingography

Laparoscopy

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Female Infertility

MENSTUAL HISTORY

BASAL BODY TEMPERATURE - Body temperature under basal condition- Procedure- Smoking forbidden- Principle: Thermogenic property of progesterone- Rise in 0.4˚to 0.8 ˚ f over the base line

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Test for ovulatory factors

Female Infertility

- Recording is biphasic in nature- Falls to lowest before ovulation & before menses

- Objective evidence of ovulation and its approx time

- BBT is still useful and may be the best method for couple who are reluctant or unable to persue more formal and costly evaluation

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PROGESTERONE CONCENTRATION

- Level remains below 1ng/ml, - rise 1-2ng/ml on the day of LH surge, - peaks 7-8 days after ovulation

- Mid luteal peak i.e day 21-23 of 28 days cycle

- Level of 3ng/ml documents ovulation

- Day of measurement: Day 21 of day 28, where ovulation occur on day 14

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Female Infertility

- Normal cycle 21-35 days, - ideal 1 week before the expected date of menses

& morning hour is the best time to test- Has been used for quality of luteal function

- There is no consensus minimum serum progesterone concentration that defines normal luteal function.

- A midluteal serum progesterone level greater than 10 ng/mL is a popular standard

- A midluteal serum progesterone concentration cannot define the quality of luteal function and has little value beyond documenting ovulation 123

Female Infertility

URINARY LH EXCRETION

- Ovulation prediction kits/ LH kits , detects mid cycle LH surge

- LH surge is a brief event lasting 48-50hours- Ovulation occurs 12-26 hours after onset of LH surge

and almost always within 48 hrs- Consequently,the interval of greatest fertility includes the

day the surge is detected and the following 2 days- Using ELISA 40mIU/ml taken as threshold

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Female Infertility

- Short half life, rapidly cleared via urine, exceed threshold level during LH surge

- Done on daily basis, beginning 2-3 days before surge is expected

- Results sensitive to volume of urine and time of day

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Female Infertility

- Based on the characteristic histological change brought about by progesterone

- Secretory endometrium implies recent ovulation- Simple office procedure- Performed on day 21-24- Pretreatment with NSAID, sedation, paracervical block- Until recently, EB to exclude luteal phase deficiency is no

longer practiced

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ENDOMETRIAL BIOPSY

Female Infertility

FOLLICULAR STUDY

- TVS monitoring of the developing dominant follicle prior to and immediately after ovum release

- Gives detailed information of size and number of pre-ovulatory follicle

- Time of test: day 12 of menses till ovulation

- Follicle reaches size upto 21-23mm( 17mm – 29mm)

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Female Infertility

- Ovulation documented: abrupt decrease in the size of follicle & ↑ fluid in the posterior cul-de-sac

- Abnormal pattern of follicular development

- ↑ at abnormal pace, collapse when follicle is still small

- Continue to grow but fail to rupture & persists as a cyst

- T/T with NSAID can disrupt ovulatory process

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Female Infertility

Test for tubal factors

HSG- Out patient procedure,

less costly, therapeutic values

- Uncomfortable and painful

- Risk of infectious complication & radiation exposure

- Images uterine cavity and reveals internal architecture of tubal lumen

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Laparoscopy- More invasive, requires GA

- Anaesthesia complication- Accidental injuries to bowel

and blood vessels

- Detailed information of pelvic anatomy including adhesion, endometriosis & ovarian pathology and their treatment

Female Infertility

HYSTEROSALPHINGOGRAPHY (HSG) - Sensitivity of 85-100% in detecting tubal diseases- Specificity of 90% in detecting PID related disease

Indication- To establish tubal patency - To diagnose developmental anomalies of uterus- Can identify submucous myoma, endometrial polyp,

intrauterine adhesionTime

- Between cycle days 6and 11 - Pretreatment: Antibiotic, NSAID

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Female Infertility

Procedure

- Vaginal cleansing- An acorn (Jascho) cannula or via ballon catheter

introduced- Contrast material is then injected

- Water soluble contrast media ( Meglumine diatrizoate, Renografin 60)

- Oil-based (Ethiodol)- Volume of contrast

- Initial 3-4ml: outline of uterine cavity- Further 5-10ml: demonstrate B/L tubal patency

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Female Infertility

Water soluble contrast

- Rapid absorption- Less risk

- Better resolution tubal architecture

- No such action

- Low

- Pregnancy rate 17%

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Oil based contrast

- Less rapid- More risk of lipid embolism,

lipid granuloma formation- Less

- Flushes out inspissated mucus & debris

- High post procedure pregnancy rate

- Pregnancy rate 33%

Female Infertility

- Image intensification fluoroscopy should be used with minimal radiation exposure

- 3 basic films are required- A scout- One to detect uterine countour & tubal patency- Post evaluation to detect area of contrast

loculation- Additional when uterus obscure tubes & uterine

cavity is abnormal

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Female Infertility

Contraindication

- Hydrosalphinx- Current PID- Cervicitis- Palpable adenexal mass- Tenderness on bimanual examination

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Female Infertility

Complication

- Infection(0.3%-1.3%)- Cx laceration- Uterine perforation- Haemorhage- Vasovagal reaction - Allergic response to dye- Radiation exposure

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Timing : should be performed within 6and 11 day of cycle .

Instruments of Hysterosalpingography:

Volsellum Higar dilator

Speculum Screw cannula Contrast media

Diagnosis: normal film. Description: small uterus (nulliparous)

1-Long thin tubal outline.2-ill defined peritoneal spillage.3-Anteverted triangular uterus, Normal size : 2.5 – 5 cm.

1

2

3

Diagnosis: normal film. Description: large uterus (multiparous)

1-Long thin tubal outline.2-ill defined peritoneal spillage.3-Anteverted triangular uterus.

1

23

Diagnosis: normal film. Description: very large uterus.

Diagnosis: retroverted uterus. Description: deviation from medline.

Diagnosis: arcuate uterus. Description: partial separation (forming right angle).

Diagnosis: unicornuate uterus. Description: one cornua , one tube , one spillage.

Diagnosis: unicornuate uterus. Description: one cornua , one tube , one spillage.

Uterus Unicornis1 tube1 uterus

Diagnosis: bicornuate uterus with filling defects. Description: differential diagnosis: fibroids , air bubbles ,

bowel gas.

Diagnosis: bilateral hydrosalpinges with patent fallopian tube.

Description: dilatation of tubes.

Diagnosis: bilateral hydrosalpinges with patent fallopian tube.

Description: saccular dilatation of tubes.

Diagnosis: uterine fibroid. Description: large, Irregular outline uterus with multiple filling

defects.

Diagnosis: Hydrosalpinx. Description: take different size and shape of dilatation

(sacculation).

Diagnosis: uterine fibroids. Description: constant filling defect (immobile).

Diagnosis: uterine fibroids. Description: constant filling defect (immobile).

Diagnosis: adenomyosis. Description: irregular outline, multiple diverticulum..

Diagnosis: small narrow uterus. Description: differential diagnosis : Asherman , DC,TB

uterus.

Case 34

Diagnosis: fallopian tube ligation. Description: absent uterine tube at both sides.

Female Infertility

LAPAROSCOPY

- Gold standard

- Indication- Abnormal HSG- Failure to conceive of normal HSG- Unexplained infertility- Age > 35years

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Female Infertility

Procedure

- Scheduling, antibiotics and risk of infection- Performed under GA, deep anesthesia or local anesthesia

- Systematic and thorough inspection of pelvis- Include uterus, anterior and posterior cul-de-sac, ovarian

surfaces and fossa and fallopian tubes

- Chromotubation: Injection of dilute dye through the cervix ( Indigo carmine dye/ methylene blue)

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Female Infertility

- Operative finding : Photographed - Can identify

- Distal tubal occlusion( fimbrial agglutination)- Pelvic or adenexal adhesion- Endometriosis

- Therapeutic- Lysis of filmsy adhesion or focal lesion- Ablation or excision of superficial

endometriosis

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Female Infertility

- Sono hysterography has better sensitivity than HSG in intrauterine lesion

- Saline sono hysterosalphingography → extension of the procedure to asses tubal patency

Timing- Proliferative phase : Endometrial polyp- Secretory phase: Submucous fibroid- Pregnancy to be ruled out

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SALINE HYSTEROSALPHINGOGRAPHY

Female Infertility

Preparation

- Pelvic infection ruled out, Prophylactic antibiotic, NSAID

- Standard Transvaginal USG carried out- Fibroid, adenexal masses, thickened endometrium- Introduction of saline through a catheter

Interpretation - Detection of saline in POD indicated tubal patency- Hysterosalphingo contrast sonography( HyCoSy)

Contrast media consisting of surfactan

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Female Infertility

TRANSVAGINAL HYDOLAPAROSCOPY AND FRETILOSCOPY

- Based on the technique COLDOSCOPYProcedure- Veres needle inserted through post. fornix ↓ LA- 200ml saline introduced, endoscope introduced- Pelvic pathology visualized

Fertiloscopy extension of hydrolaparoscoy, endoscope is introduced through fimbrial end

- Allows visualization of tubal ostial spasm, Abn tubal mucosal pattern, intraluminal debris

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Female Infertility

3 basic methods: HSG, TVS, Saline/ contrast sonohysterography

TRANSVAGINAL USG- Modern transducers produce high resolution images - Endovaginal probes yield details of

- Uterus, ovaries or adenexal pathology- Fallopian tubes cannot be visualised

- Saline sonohysterosalphingography performed

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Test for uterine factors

Female Infertility

Indication

- Identification of congenital malformation- Septate, bicornuate, unicornuate, didelphus- Adenexal mass- Endometrial polyp, submucous fibroid- Intrauterine adhesion

Timing- In all phases of the cycle

Diagnostic accuracy can be compared with hysteroscopy

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Female Infertility

HYSTEROSCOPY

- Gold standard for diagnosis & treatment

Indication

- Abnormal HSG/ TVS: Endometrial polyp, myoma, uterine septum or intrauterine adhesions

- Unexplained infertility- Recurrent spontaneous abortion

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Female Infertility

Procedure

- Performed as office procedure

- Prior administration of intravaginal Misoprostol 200µg

- In infertility, best initial choice for diagnosis and treatment of suspicious intrauterine lesion

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Female Infertility

Therapeutic

- Endometrial polyp: Polypectomy- Submucous fibroid: Hysteroscopic myomectomy- Uterine septum: Division- Intrauterine adhesion: Adhesiolysis

Unmedicated IUD / ballon catheter

Estrogen therapy 2 months

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Female Infertility

POST COITAL TEST ( SIMS – HUNNER TEST)Objective- To assess quality of cervical mucous- To assess presence of number or motile sperm- To see interaction between Cx mucous and sperm

Prerequisite- Absteinence for 48hrs, no lubricants, douching, medications- Performed shortly before ovulation, examined within 2-

12hours of coitus- The post coital test for diagnosis of cervical factor is no longer

recommended

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Test for cervical factor

Female Infertility

Cervical mucous study

- Volume : copius and thin- Clearity : watery and clear- PH: 6.8 - 7.4 at the time of ovulation- Cellularity:- Viscosity: Spinnbarkeit , length that can be stretched

10cm- Salinity: Fern pattern, complexity of network of crystal- Poor quality: Improper timing, cervicitis, CIN, anti

estrogens like chlomiphene citrate

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Female Infertility

Presence of no. of motile sperm

- Presence one motile sperm/hpf in most fields → normal- Confirms effective coital technique and survival- Motile sperm predicts normal semen quality- Negative results

- Ineffective coital technique- Failed ejaculation- Poor semen quality- Use of lubricants/spermicide

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Female Infertility

Interaction between cervical mucous and sperm

- Presence of >25% sperm exhibiting shaking and jerky movement / immotile sperm→ Anti sperm antibodies

Test for antisperm antibodies- Sperm agglutination test- Sperm compliment dependant immobilization- Immunobead test- Mixed agglutination test

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Thank you