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APPROACH TO FEMALE INFERTILIY .pptx

1. The document discusses an approach to evaluating and treating female infertility. It defines infertility, discusses its prevalence and causes, and outlines evaluations including medical history, physical exam, and diagnostic testing. 2. Evaluation of both partners is recommended to identify potential causes of infertility such as ovulatory disorders, diminished ovarian reserve, tubal factors, and uterine abnormalities. 3. Prepregnancy counseling and optimizing chronic conditions are also discussed to maximize outcomes for patients seeking pregnancy. A comprehensive female evaluation incorporates history, exam, and testing to determine diagnosis and appropriate treatment.

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APPROACH TO FEMALE INFERTILITY DR. VANDANA BANSAL MS, D.phil. (Gold Medalist), DGO, FCGP Infertility & IVF Specialist & Advance Laparoscopic and hysteroscopic Surgeon DIRECTOR Arpit Test Tube Baby Centre, Prayagraj Jeevan Jyoti Hospital, Prayagraj (U.P.)
The problem of infertility or sterility is as old as human evolution. A couple without a child is a barren wedlock leading to unhappiness and frustration in life. Infertility is a public health problem associated with medical and social consequences. Adding to the emotional and physical toll exacted by infertility is the financial burden during extensive work-up and treatment. Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and medical detriments to the patient. Data indicate that ART has increase 5-10% annually INTRODUCTION “Human fertility is on the decline in the modern era”
How do we define infertility Failure to achieve a successful pregnancy after ≥ 12 months of regular, unprotected sexual intercourse or because of impairment of the capacity to reproduce either as an individual or with a partner.  Under 35 year :No conception after one year of unprotected intercourse  Over 35 year :No conception after 6 months of unprotected intercourse Sub-fertility, Involuntary infertility 1. Primary infertility - a couple that has never conceived. 2. Secondary infertility - infertility that occurs after previous pregnancy regardless of outcome Fifteen studies supplied estimates of primary and secondary infertility occurrence in 6400 infertile couple. Out of 6400 infertile patients 3600 (56.25%) imparting with number one and 2800 (43.2%) imparting with secondary infertility. INFERTILITY
Why we are worried? Factors in Male & Female both 15% Unexplained 10 to 15% Worldwide 60-80 million couple have infertility For couple in 30-35 age group, it is 1 in 7 couple. For couple in 35-40 age group, it is 1 in 5 couple. For couple in 40-45 age group, it is 1 in 4 couple. Worldwide, infertility rates are higher in Eastern Europe, North Africa, and the Middle East. Worldwide,2% of women aged 20 to 44 were never able to have a live birth, and 11% with a previous live birth were unable to have an additional birth BURDEN OF INFERTILITY
Is infertility on rise? • Late marriage • Delay child bearing • Rise in live in relationship • Stressful lifestyle- environmental toxins, Radiation • Obesity • High junk food intake • Smoking • Alcohol • Drug-addiction
How does Age affects a woman's ability to have children? Age of women is very important factor in deciding modality of infertility. treatment Primitive germ cells provide 1 to 2 million oocytes in the ovaries at birth At puberty, this number is reduced through cell death to approximately 300,000 With increasing age quality and quantity of oocytes decrease Aging oocytes leads to ↓ Pregnancy rate ↑ Miscarriage rate ↑ Risk of chromosomal problems, like Down’s syndrome ↑ Obstetrical complications like PIH and Diabetes Fertility declines after 30 years, further after 35 years and grossly after 40 years Decreased in oocyte quantity Enhanced follicular atresia Increased rate of chromosomal abnormalities.
• Ovulatory disorders - 25% • Endometriosis - 15% • Pelvic adhesions - 12% • Tubal blockage - 11% • Other tubal/uterine abnormalities - 11% • Hyperprolactinemia - 7% In a study of 8500 infertile couples done by the World Health Organization (WHO) The most common identifiable female factors which accounted for 81 percent of female infertility, included: CAUSES OF FEMALE INFERTILITY
Pelvic factors 1.Congenital malformation of the reproductive system, - Müllerian duct aplasia 2. Cervical factors, -Anatomical, Cervical Tear, - cervical insufficiency & diseases, Erosion, Polyp - Anti-sperm antibodies. 3. Uterine disorder - endometrial lesions,( tuberculous endometritis, polyps etc) - uterine tumors,(fibroids), Adenomyosis - Endometrium-thin, hyperplastic - intrauterine adhesions(Asherman’s syndrome,) 4. Oviduct and its surrounding disorders, - oviduct obstruction, - peritubal adhesions, - hydrosalpinx, and - pelvic adhesion 5. Endometriosis. Tubal factors Congenital absence of both tubes Bilateral tubal obstruction causing endosalpingitis or perisalpingitis. • PID : Genital Tuberculosis, Post gonococcal, Pyogenic infection • Pelvic endometriosis • Post operative adhesions producing bilateral obstructions. • Tubectomy Vaginal Causes of Infertility • Imperforate hymen • Blockage of the vagina • Extremely narrow vagina • Painful infections in the vagina • Vaginismus • Immunological CAUSES OF FEMALE INFERTILITY
World Health Organization subdivided ovulatory disorders into four classes: 1. Hypogonadotropic hypogonadal anovulation: i.e., hypothalamic amenorrhea 2. Normogonadotropic normoestrogenic anovulation: i.e., polycystic ovarian syndrome (PCOS) 3. Hypergonadotropic hypoestrogenic anovulation: i.e., premature ovarian failure 4. Hyperprolactinemic anovulation: i.e., pituitary adenoma Ovulatory dysfunction (defined as a history of oligomenorrhea or amenorrhea or as luteal progesterone levels repeatedly less than 3 ng/mL, or both) accounts for a significant proportion of female infertility OVULATORY DYSFUNCTION
Evaluation of Infertile Couple • Both partner should be seen evaluated and treated Simultaneously • Couple evaluation has positive phycological benefits • The protocol vary from country to country and institution to institution • Based on the history and clinical examination the next diagnostic evaluation should be carried out in a systematically which should also be cost effective to come to definite cause of infertility. • The endpoint should be shifted from conception to live birth.
The American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) make the following recommendations. An infertility evaluation may be offered to any patient who by definition has infertility or is at high risk of infertility. • Women older than 35 years should be evaluated and undergo treatment after 6 months of failure to conceive or earlier. • women older than 40 years, immediate evaluation and treatment warranted. • If a woman has a condition known to cause infertility, immediate evaluation. • Comprehensive medical history ,including relevant to the potential etiologies of infertility .should be obtained from both partner, • Targeted physical examination of the female partner with a focus on vital signs • Including a thyroid, breast, and pelvic examination. • Focus on evaluation of ovarian reserve, ovulatory function, and structural abnormalities • Imaging modalities to detect tubal patency and pelvic pathology and assess ovarian reserve. To obtain the male partner’s medical history and evaluate semen analysis parameter or refer male infertility patients to expert specialist in male reproductive EVALUATION
Indications for earlier or immediate evaluation include the following: • Oligomenorrhea or amenorrhea • Known or suspected uterine, tubal, or peritoneal disease • Stage III or stage IV endometriosis and • Known or suspected male infertility • Women over 35 Year
• History • Physical • Prepregnancy evaluation • Additional evaluation for etiology of infertility • Diminished ovarian reserve - Antimullerian hormone or basal follicle-stimulating hormone plus estradiol -Transvaginal ultrasonography with antral follicle count • Ovulatory dysfunction - Ovulatory function test (eg, serum progesterone measurement) • Tubal factor - Hysterosalpingography - Hysterosalpingo-contrast sonography • Uterine factor - Transvaginal ultrasonography - Sonohysterography - Hysteroscopy - Hysterosalpingography APPROCH TO FEMALE EVALUATION
• Whether the reproductive-aged patient is currently using contraception or planning pregnancy. • Prepregnancy counseling should occur several times during a woman's reproductive lifespan, because health status and risk factors can change over time maximizing her reproductive and pregnancy outcomes. • Chronic medical conditions such as diabetes, hypertension, psychiatric illness, and thyroid disease have implications for pregnancy outcomes and should be optimally managed before pregnancy. Recommendations for screening-  Sexually transmitted infection  Screening for the same genetic conditions as recommended for pregnant women.  All patients should be routinely asked about their use of alcohol, nicotine products, and drugs, including prescription opioids and other medications used for nonmedical reasons.  Female Prepregnancy folic acid supplementation should be encouraged to reduce the risk of neural tube defects.  Role of micro-nutrient & Diet PREPREGNANCY EVALUATION
• Duration of infertility - Past treatment history - Menstrual history • Previous any pregnancy history - Past contraception use - History of sexual dysfunction • Previous surgical history - Hospitalizations history - Pelvic inflammatory disease - Medical history like thyroid disease, galactorrhea, and hirsutism • History of abnormal Pap smears - Family history of congenital defect • History of occupation - addiction to any substances RELEVANT HISTORY
Examination of Female partner General Examination : • Presence of features of syndromes : Turner’s syndrome, Cushing’s syndrome. • Second sexual characters: Hirsutism, Presence of acne • Severe pallor • Breasts for galactorrhea, thyroid • Signs of tuberculosis : scars, sinuses Local examination: Perform per speculum & per vaginal examinations for any obvious abnormalities. • Imperforate or rigid hymen, Vaginismus • Malformation-aplasia or hypoplasia of uterus • Aplasia of vagina, trasverse vaginal septum • Adnexal masses (PCOS, pelvic inflammatory disease masses: tubercular, gonococcal; ovarian tumors) • Uterine enlargement multiple leiomyomas • Signs suggestive of pelvic endometriosis (uterosacral nodularity) Examination Under Transvaginal Sonography (TVS): To compliment and confirm
Counselling of infertile couple • Couple’s interview is conducted together as well as separately • Psychological counselling - at various levels • Counselling by trained personnel. • Scoring system : A B C • Preparation for the procedure • Clinical counselling • Discuss diagnosis, • Plan of treatment with duration, • Treatment options, • Success rate of procedure. • OPD • Procedure: • Pre-procedure, Procedure, Post-procedure - Related Counselling & Consent • Documentation: • Written, Video, Special cases separate consent - on stamp paper & can be notarized
Evaluation of Male Partner • General physical examination and medical history • Semen analysis. • Scrotal ultrasound • Hormone testing • Post-ejaculation urinalysis( to rule out retrograde ejaculation). • Genetic tests • Testicular biopsy. • Specialized sperm function tests
Preliminary fertility investigations Day 2-4 follicle-stimulating hormone, luteinising hormone, oestradiol Anti-Mullerian hormone Thyroid stimulating hormone Transvaginal ultrasonography of the pelvis: antral follicle count, pelvic anatomy and features of deep infiltrating endometriosis Blood group and antibody screen Full blood examination Rubella, varicella immunoglobulin G Hepatitis B, hepatitis C, human immunodeficiency virus and syphilis serology Genetic carrier screening if desired: thalassaemia, triple screen (fragile X syndrome, cystic fibrosis, spinal muscular atrophy), extended carrier screen
Transvaginal ultrasonography •Baseline scan- done in day 2 or day 3 of menstrual cycle. It Measure the Ovarian size and volume,Ovarian Position, any cyst / pathology of Adnexa, Antral follicle count(Low antral follicle count may be defined as fewer than 5–7 follicles, With poor response to ovarian stimulation, AFC may be elevated in women with polycystic ovary syndrome(PCOS)) •Preovulatory scan- Day 9 or 10 of natural or IUI cycle, Day 5 or 6 of IVF cycle and serial scan •Luteal phase scan- Assessment of the Rupture of follicle, establish the presence of an adequately functioning corpus luteum, luteal blood flow in Color Doppler with R.I 0.35-0.50 and PSV10-15. •TVS is also a very good predictor for the prediction of different physiological changes undergoing at the level of endometrium during pre-ovulatory and luteal phase of the cycle • 3D USG Ovulation Induction is monitored to Identify Ovarian response in natural cycle, IUI cycle and IVF Cycle. MATURE DOMINANT FOLLICLE IN 2D AND COLOR DOPLER •In stimulated cycles (IUI / IVF) it helps check if the ovulation stimulation is optimum, whether the parameters suggest a cycle to be cancelled, and also decide the timing for trigger.
• Basal body temperature • Cervical mucus study: Fern test • Spinnbarkeit test • Vaginal cytology • Endometrial biopsy • Midluteal S progesterone A concentration greater than 3.0 ng/mL in a blood sample drawn between days 19 and 23 is consistent with ovulation, whereas a concentration greater than 10 ng/mL implies adequate luteal support. • ovulation predictor Kits (Detect LH Surge)- detects a rise in luteinizing hormone (LH) in the urine, begin testing 3 to 5 days prior to the expected date of ovulation. positive result means that ovulation will be in the next 24 to 36 hours. • Ultrasonography- TVS & Color Doppler. OVULATION PREDICTORS
INVESTIGATIONS LAB INVESTIGATIONS DIAGNOSTIC APPROACH EVALUATION OVULATORY Evaluation of peripheral or end-organ changes • Basal Body Temperature • Cervical mucus study • Vaginal cytology • Hormone estimation - Serum progesterone — Serum LH - Urine LH - Serum estradiol - Endometrial biopsy History, Physical examination and basic investigation ANOVULATORY CYCLES Endocrine evaluation (FSH, LH, DHEA-S TSH, Prolactin) TUBAL AND UTERINE FACTORS CERVICAL FACTORS Postcoital test for immunological factor Endometrial biopsy Hysterosalpingography Hystero-salpingo- contrast sonography Laparoscopy and dye hydrotubation test and hysteroscopy
Anovulatory cycles Endocrine evaluation (FSH, LH, DHEA-S TSH, Prolactin) DHEA-S LH, FSH, AMH FSH, LH LH, FSH TSH Prolactin Adrenal disease Polycystic Ovarian syndrome Premature ovarian failure or resistant Ovarian syndrome Hypogonadotropic hypogonadism Hypothyroidism Prolactinoma Testosterone, DHEA-S, 17-Hydroxyprogesterone
Ovarian Reserve Testing ovarian reserve, represents the number of oocytes available for potential fertilization at that point in time and may be assessed by serum tests or ultrasonography. 1. Age 2. AMH 3. AFC Day #3 FSH (<10 mIU/ml) and estradiol (<80 pg/ml) -Correlates with the functional status of the ovaries and the quality of the oocytes - FSH >15 only 5% success with IVF - High estradiol level increases risk of cancelling IVF cycle Ovarian reserve tests are good predictors of response to ovarian stimulation, but poor results do not necessarily predict inability to achieve a live birth.
Diminished Ovarian Reserve The presence of decreased ovarian reserve predicts future response to ovarian stimulation Although there are no definitive criteria for diminished ovarian reserve, the following values may be considered consistent with diminished ovarian reserve: • Antimullerian hormone (AMH) value less than 1 ng/mL • antral follicle count less than 5–7 and • follicle-stimulating hormone (FSH) greater than 10 IU/L or • a history of poor response to in vitro fertilization stimulation (fewer than four oocytes at time of egg retrieval).
Most common type of Normogonadotropic normoestrogenic anovulation is PCOS. • PCOS accounts for 80 to 85% • 8% of all reproductive-aged females. • PCOS can be diagnosed using the. Rotterdam criteria for PCOS, which requires at least two of the three below listed criteria in the absence of other pathological causes. • Oligoovulation/anovulation • Clinical signs of hyperandrogenism and/or serological elevations of androgens • Polycystic ovaries demonstrated with ultrasound • PCOS is a diagnosis of exclusion PCOD
Hysterosalpingography (HSG) Chlamydia Antibody Test Assesses shape of the uterine cavity-Evaluates Tubal Less invasive and cost effective Assessment of tubal abnormalities - Tubal occlusion - Tubal irregularity - Peritubal Abnormalities HSG: Hydrosalpinx HSG: Unilateral Blocked Tube Arcuate uterus Intrauterine adhesions • Tubal spasm • Only 38% tubal blockage is confirm by laparoscopy • More specific for detecting distal tubal occlusion • Diagnostic And Therapeutic specially with oil based media. The positive predictive value and negative predictive value of HSG for assessing tubal patency have been estimated as 38% and 94%, respectively TUBAL EVALUATION
Sonohysterography is the visualization of the uterus and adnexa ultrasonographically with the infusion of fluid through a transcervical catheter Using sonohysterography, the uterine cavity usually is easily defined, and abnormalities such as endometrial polyps, submucosal fibroids, and intrauterine adhesions can be seen. More than 16% of infertile women and 40% of women with abnormal uterine bleeding will have an abnormality on sonohysterography . Sonohysterography has a sensitivity and specificity of 91% and 84%, respectively, for the detection of intrauterine structures HyCoSy (hysterosalpingo contrast sonography) - with automated 3D-coded contrast imaging technology. Laparoscopy with chromopertubation Tubal evaluation Hysterosalpingo-contrast sonography (HyCoSy)
Other Tests  Hysteroscopic evaluation  To evaluate condition of uterine  Cavity (polyps, fibroids(sub-mucus), intra cavitary lesion, intra uterine adhesion( uterine synechiae), Mullerian duct anomalies(uterine septum) Endometritis  Laparoscopic evaluation  Although considered as gold standard not taken as routine investigation these days.  Check patency of fallopian tubes specially in unexplained infertility .  Tubal adhesions  To evaluate for pelvic disease,  Endometriosis (grading & Treatment)  Ovarian Pathology or uterine fibroid distorting cavity.  Mullerian anomalies
INDICATION OF MRI IN FEMALE INFERTILITY • Complex adnexal masses • Endometriosis deep seated • Mullerian duct anomalies • Adenomyosis • Fibroids- Pre surgical mapping of location and vascularity of fibroid. • Intra uterine adhesion • Pyosalpinx • Cornual fibroid MRI is superior to USG in determining both tubal and peritubal component of PID. In the era of evidence based medicine. MRI has on indispensable role in diagnosis & management of female infertility Non-invasive radiation free modality
• Laparoscopy for unexplained infertility • Advanced sperm function testing (eg, DNA fragmentation testing) • Postcoital testing • Thrombophilia testing • Immunologic testing • Karyotype • Endometrial biopsy • Prolactin Infertility test that should not be routinely ordered
Unexplained infertility may be diagnosed in as many as 19-20% of infertile couples the basic infertility evaluation is performed, and all the tests results are normal. At a minimum, these patients have evidence of ovulation, tubal patency, and a normal semen analysis UNEXPLAINED INFERTILITY • For most couples with unexplained infertility, the best initial therapy is a course (typically 3 or 4 cycles) of OS and IUI, either with clomiphene or letrozole, followed by IVF for those couples unsuccessful in achieving a pregnancy with OS and IUI. • There is a pressing need for additional therapies to bridge the wide gap in effectiveness between OS and IUI with oral medications and IVF. • Further research is needed into methods to improve access to care, including ART treatments.
Environmental toxins affecting fertility • Pesticides • Mercury • Lead • Cadmium • Bisphenol- A • Flame retardance • Phthalates
• Age • Duration of infertility • Cause of infertility • Financial resources • Sperm concentration in the sample In treatment main deciding factor are: Factors affecting modality of infertility treatment
Lifestyle Changes The ideal BMI for getting pregnant is between 18.5 and 24.9. Diet and Exercise • Women with extremes in body mass index (BMI) frequently present with infertility and ovulatory dysfunction. • Women with a BMI of less than 17 kg/m^2 with a history of intense exercise regimens or women with eating disorders are likely to develop hypogonadotropic hypogonadism, which causes deceased pituitary gonadotropin secretions • Women with a BMI greater than 27 kg/m^2 with anovulation can improve ovulation with weight loss alone. Multiple studies have shown that a loss of 10% of body weight will restore normal ovulation in 50 to 100% of women in less than 1 year . • Bariatric surgery Treatment / Management
Infertility Period APPROACH TO TREATMENT ALGORITHM
APPROACH TO TREATMENT ALGORITHM Age Factor
Treatment options… Overcoming Infertility Nearly 90% of all infertility cases, both male and female factor, all can be treated . Treatment options are: • Expectant Treatment • Ovulation Induction & COH • Medical & Surgical treatment of Male • Laparoscopic & Hysteroscopic Surgery for Female • Intrauterine Insemination (IUI)
When to attempt IUI First • At least one unblocked fallopian tube • Able to ovulate, perhaps with the help of fertility medications • Healthy ovarian reserve, good amount of healthy eggs • Normal uterine cavity • Cervical issue scarring/hostile cervix may block fertilization • Mild ovulation issue like polycystic ovarian syndrome (PCOS) • Donor sperm • Mild to moderate male factor • After male fertility preservation before cancer treatment or surgery • Same sex couple
Intra-Uterine Insemination (IUI) • First line of treatment provided both or either one fallopian tubes are patent. specially in pt under age of 35 years • Simple, Non-Invasive & Cost Effective • IUI is a viable option before proceeding to ART • Processed total motile sperm(PTMS)>1 million/ml • Progressive motility >30%, morphology >4%, is the most important criteria. Sperm survival <70% • Prewash IUI semen pregnancy score (IUI-SPS)<150 • IUI+ mild COH- gives good pregnancy rate • Clinical pregnancy rate per cycle is 10-20%
8 Tips for fertility wellness • Decrees stress • Solid 8 hours of sleep • Practice mindful eating • Cultivate supportive network • Balance being and doing fertile window • Regular Exercise but not excessive • Treat each day as new opportunity • Meditation (Can be done with brahma Kumari)
Timely Referral To Specialist Care
Summary • There are potential consequences of delayed, later-age referral to a reproductive endocrinology and infertility (REI) specialist • Diagnostic tests are conducted after - 1 year of infertility for woman aged <35 years - 6 months of infertility for woman aged > 35 years • The Ob/Gy fertility specialist and patient need to work together to determine reasonable expectations and optimal treatment course • Due to new ART laws early child bearing should be promoted and fertility preservation by egg freezing should be done in case of delayed marriage and child bearing. • Diagnostic laparoscopy is no more a routine investigation for tubal testing. • Role of color doppler and 3D ultrasound is promising. • Role of MRI in fibroid, complex ovarium masses and PID is increasing. • The endpoint should be shifted from conception to live birth. • Evaluation should be done systematically which should also be cost effective to come to definite cause of infertility. 43
APPROACH TO FEMALE INFERTILIY .pptx

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APPROACH TO FEMALE INFERTILIY .pptx

  • 1.
    APPROACH TO FEMALEINFERTILITY DR. VANDANA BANSAL MS, D.phil. (Gold Medalist), DGO, FCGP Infertility & IVF Specialist & Advance Laparoscopic and hysteroscopic Surgeon DIRECTOR Arpit Test Tube Baby Centre, Prayagraj Jeevan Jyoti Hospital, Prayagraj (U.P.)
  • 2.
    The problem ofinfertility or sterility is as old as human evolution. A couple without a child is a barren wedlock leading to unhappiness and frustration in life. Infertility is a public health problem associated with medical and social consequences. Adding to the emotional and physical toll exacted by infertility is the financial burden during extensive work-up and treatment. Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and medical detriments to the patient. Data indicate that ART has increase 5-10% annually INTRODUCTION “Human fertility is on the decline in the modern era”
  • 3.
    How do wedefine infertility Failure to achieve a successful pregnancy after ≥ 12 months of regular, unprotected sexual intercourse or because of impairment of the capacity to reproduce either as an individual or with a partner.  Under 35 year :No conception after one year of unprotected intercourse  Over 35 year :No conception after 6 months of unprotected intercourse Sub-fertility, Involuntary infertility 1. Primary infertility - a couple that has never conceived. 2. Secondary infertility - infertility that occurs after previous pregnancy regardless of outcome Fifteen studies supplied estimates of primary and secondary infertility occurrence in 6400 infertile couple. Out of 6400 infertile patients 3600 (56.25%) imparting with number one and 2800 (43.2%) imparting with secondary infertility. INFERTILITY
  • 4.
    Why we areworried? Factors in Male & Female both 15% Unexplained 10 to 15% Worldwide 60-80 million couple have infertility For couple in 30-35 age group, it is 1 in 7 couple. For couple in 35-40 age group, it is 1 in 5 couple. For couple in 40-45 age group, it is 1 in 4 couple. Worldwide, infertility rates are higher in Eastern Europe, North Africa, and the Middle East. Worldwide,2% of women aged 20 to 44 were never able to have a live birth, and 11% with a previous live birth were unable to have an additional birth BURDEN OF INFERTILITY
  • 5.
    Is infertility onrise? • Late marriage • Delay child bearing • Rise in live in relationship • Stressful lifestyle- environmental toxins, Radiation • Obesity • High junk food intake • Smoking • Alcohol • Drug-addiction
  • 6.
    How does Ageaffects a woman's ability to have children? Age of women is very important factor in deciding modality of infertility. treatment Primitive germ cells provide 1 to 2 million oocytes in the ovaries at birth At puberty, this number is reduced through cell death to approximately 300,000 With increasing age quality and quantity of oocytes decrease Aging oocytes leads to ↓ Pregnancy rate ↑ Miscarriage rate ↑ Risk of chromosomal problems, like Down’s syndrome ↑ Obstetrical complications like PIH and Diabetes Fertility declines after 30 years, further after 35 years and grossly after 40 years Decreased in oocyte quantity Enhanced follicular atresia Increased rate of chromosomal abnormalities.
  • 7.
    • Ovulatory disorders- 25% • Endometriosis - 15% • Pelvic adhesions - 12% • Tubal blockage - 11% • Other tubal/uterine abnormalities - 11% • Hyperprolactinemia - 7% In a study of 8500 infertile couples done by the World Health Organization (WHO) The most common identifiable female factors which accounted for 81 percent of female infertility, included: CAUSES OF FEMALE INFERTILITY
  • 8.
    Pelvic factors 1.Congenital malformationof the reproductive system, - Müllerian duct aplasia 2. Cervical factors, -Anatomical, Cervical Tear, - cervical insufficiency & diseases, Erosion, Polyp - Anti-sperm antibodies. 3. Uterine disorder - endometrial lesions,( tuberculous endometritis, polyps etc) - uterine tumors,(fibroids), Adenomyosis - Endometrium-thin, hyperplastic - intrauterine adhesions(Asherman’s syndrome,) 4. Oviduct and its surrounding disorders, - oviduct obstruction, - peritubal adhesions, - hydrosalpinx, and - pelvic adhesion 5. Endometriosis. Tubal factors Congenital absence of both tubes Bilateral tubal obstruction causing endosalpingitis or perisalpingitis. • PID : Genital Tuberculosis, Post gonococcal, Pyogenic infection • Pelvic endometriosis • Post operative adhesions producing bilateral obstructions. • Tubectomy Vaginal Causes of Infertility • Imperforate hymen • Blockage of the vagina • Extremely narrow vagina • Painful infections in the vagina • Vaginismus • Immunological CAUSES OF FEMALE INFERTILITY
  • 9.
    World Health Organizationsubdivided ovulatory disorders into four classes: 1. Hypogonadotropic hypogonadal anovulation: i.e., hypothalamic amenorrhea 2. Normogonadotropic normoestrogenic anovulation: i.e., polycystic ovarian syndrome (PCOS) 3. Hypergonadotropic hypoestrogenic anovulation: i.e., premature ovarian failure 4. Hyperprolactinemic anovulation: i.e., pituitary adenoma Ovulatory dysfunction (defined as a history of oligomenorrhea or amenorrhea or as luteal progesterone levels repeatedly less than 3 ng/mL, or both) accounts for a significant proportion of female infertility OVULATORY DYSFUNCTION
  • 10.
    Evaluation of InfertileCouple • Both partner should be seen evaluated and treated Simultaneously • Couple evaluation has positive phycological benefits • The protocol vary from country to country and institution to institution • Based on the history and clinical examination the next diagnostic evaluation should be carried out in a systematically which should also be cost effective to come to definite cause of infertility. • The endpoint should be shifted from conception to live birth.
  • 11.
    The American Collegeof Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) make the following recommendations. An infertility evaluation may be offered to any patient who by definition has infertility or is at high risk of infertility. • Women older than 35 years should be evaluated and undergo treatment after 6 months of failure to conceive or earlier. • women older than 40 years, immediate evaluation and treatment warranted. • If a woman has a condition known to cause infertility, immediate evaluation. • Comprehensive medical history ,including relevant to the potential etiologies of infertility .should be obtained from both partner, • Targeted physical examination of the female partner with a focus on vital signs • Including a thyroid, breast, and pelvic examination. • Focus on evaluation of ovarian reserve, ovulatory function, and structural abnormalities • Imaging modalities to detect tubal patency and pelvic pathology and assess ovarian reserve. To obtain the male partner’s medical history and evaluate semen analysis parameter or refer male infertility patients to expert specialist in male reproductive EVALUATION
  • 12.
    Indications for earlieror immediate evaluation include the following: • Oligomenorrhea or amenorrhea • Known or suspected uterine, tubal, or peritoneal disease • Stage III or stage IV endometriosis and • Known or suspected male infertility • Women over 35 Year
  • 13.
    • History • Physical •Prepregnancy evaluation • Additional evaluation for etiology of infertility • Diminished ovarian reserve - Antimullerian hormone or basal follicle-stimulating hormone plus estradiol -Transvaginal ultrasonography with antral follicle count • Ovulatory dysfunction - Ovulatory function test (eg, serum progesterone measurement) • Tubal factor - Hysterosalpingography - Hysterosalpingo-contrast sonography • Uterine factor - Transvaginal ultrasonography - Sonohysterography - Hysteroscopy - Hysterosalpingography APPROCH TO FEMALE EVALUATION
  • 14.
    • Whether thereproductive-aged patient is currently using contraception or planning pregnancy. • Prepregnancy counseling should occur several times during a woman's reproductive lifespan, because health status and risk factors can change over time maximizing her reproductive and pregnancy outcomes. • Chronic medical conditions such as diabetes, hypertension, psychiatric illness, and thyroid disease have implications for pregnancy outcomes and should be optimally managed before pregnancy. Recommendations for screening-  Sexually transmitted infection  Screening for the same genetic conditions as recommended for pregnant women.  All patients should be routinely asked about their use of alcohol, nicotine products, and drugs, including prescription opioids and other medications used for nonmedical reasons.  Female Prepregnancy folic acid supplementation should be encouraged to reduce the risk of neural tube defects.  Role of micro-nutrient & Diet PREPREGNANCY EVALUATION
  • 15.
    • Duration ofinfertility - Past treatment history - Menstrual history • Previous any pregnancy history - Past contraception use - History of sexual dysfunction • Previous surgical history - Hospitalizations history - Pelvic inflammatory disease - Medical history like thyroid disease, galactorrhea, and hirsutism • History of abnormal Pap smears - Family history of congenital defect • History of occupation - addiction to any substances RELEVANT HISTORY
  • 16.
    Examination of Femalepartner General Examination : • Presence of features of syndromes : Turner’s syndrome, Cushing’s syndrome. • Second sexual characters: Hirsutism, Presence of acne • Severe pallor • Breasts for galactorrhea, thyroid • Signs of tuberculosis : scars, sinuses Local examination: Perform per speculum & per vaginal examinations for any obvious abnormalities. • Imperforate or rigid hymen, Vaginismus • Malformation-aplasia or hypoplasia of uterus • Aplasia of vagina, trasverse vaginal septum • Adnexal masses (PCOS, pelvic inflammatory disease masses: tubercular, gonococcal; ovarian tumors) • Uterine enlargement multiple leiomyomas • Signs suggestive of pelvic endometriosis (uterosacral nodularity) Examination Under Transvaginal Sonography (TVS): To compliment and confirm
  • 17.
    Counselling of infertilecouple • Couple’s interview is conducted together as well as separately • Psychological counselling - at various levels • Counselling by trained personnel. • Scoring system : A B C • Preparation for the procedure • Clinical counselling • Discuss diagnosis, • Plan of treatment with duration, • Treatment options, • Success rate of procedure. • OPD • Procedure: • Pre-procedure, Procedure, Post-procedure - Related Counselling & Consent • Documentation: • Written, Video, Special cases separate consent - on stamp paper & can be notarized
  • 18.
    Evaluation of MalePartner • General physical examination and medical history • Semen analysis. • Scrotal ultrasound • Hormone testing • Post-ejaculation urinalysis( to rule out retrograde ejaculation). • Genetic tests • Testicular biopsy. • Specialized sperm function tests
  • 19.
    Preliminary fertility investigations Day2-4 follicle-stimulating hormone, luteinising hormone, oestradiol Anti-Mullerian hormone Thyroid stimulating hormone Transvaginal ultrasonography of the pelvis: antral follicle count, pelvic anatomy and features of deep infiltrating endometriosis Blood group and antibody screen Full blood examination Rubella, varicella immunoglobulin G Hepatitis B, hepatitis C, human immunodeficiency virus and syphilis serology Genetic carrier screening if desired: thalassaemia, triple screen (fragile X syndrome, cystic fibrosis, spinal muscular atrophy), extended carrier screen
  • 20.
    Transvaginal ultrasonography •Baseline scan-done in day 2 or day 3 of menstrual cycle. It Measure the Ovarian size and volume,Ovarian Position, any cyst / pathology of Adnexa, Antral follicle count(Low antral follicle count may be defined as fewer than 5–7 follicles, With poor response to ovarian stimulation, AFC may be elevated in women with polycystic ovary syndrome(PCOS)) •Preovulatory scan- Day 9 or 10 of natural or IUI cycle, Day 5 or 6 of IVF cycle and serial scan •Luteal phase scan- Assessment of the Rupture of follicle, establish the presence of an adequately functioning corpus luteum, luteal blood flow in Color Doppler with R.I 0.35-0.50 and PSV10-15. •TVS is also a very good predictor for the prediction of different physiological changes undergoing at the level of endometrium during pre-ovulatory and luteal phase of the cycle • 3D USG Ovulation Induction is monitored to Identify Ovarian response in natural cycle, IUI cycle and IVF Cycle. MATURE DOMINANT FOLLICLE IN 2D AND COLOR DOPLER •In stimulated cycles (IUI / IVF) it helps check if the ovulation stimulation is optimum, whether the parameters suggest a cycle to be cancelled, and also decide the timing for trigger.
  • 21.
    • Basal bodytemperature • Cervical mucus study: Fern test • Spinnbarkeit test • Vaginal cytology • Endometrial biopsy • Midluteal S progesterone A concentration greater than 3.0 ng/mL in a blood sample drawn between days 19 and 23 is consistent with ovulation, whereas a concentration greater than 10 ng/mL implies adequate luteal support. • ovulation predictor Kits (Detect LH Surge)- detects a rise in luteinizing hormone (LH) in the urine, begin testing 3 to 5 days prior to the expected date of ovulation. positive result means that ovulation will be in the next 24 to 36 hours. • Ultrasonography- TVS & Color Doppler. OVULATION PREDICTORS
  • 22.
    INVESTIGATIONS LAB INVESTIGATIONS DIAGNOSTICAPPROACH EVALUATION OVULATORY Evaluation of peripheral or end-organ changes • Basal Body Temperature • Cervical mucus study • Vaginal cytology • Hormone estimation - Serum progesterone — Serum LH - Urine LH - Serum estradiol - Endometrial biopsy History, Physical examination and basic investigation ANOVULATORY CYCLES Endocrine evaluation (FSH, LH, DHEA-S TSH, Prolactin) TUBAL AND UTERINE FACTORS CERVICAL FACTORS Postcoital test for immunological factor Endometrial biopsy Hysterosalpingography Hystero-salpingo- contrast sonography Laparoscopy and dye hydrotubation test and hysteroscopy
  • 23.
    Anovulatory cycles Endocrine evaluation (FSH,LH, DHEA-S TSH, Prolactin) DHEA-S LH, FSH, AMH FSH, LH LH, FSH TSH Prolactin Adrenal disease Polycystic Ovarian syndrome Premature ovarian failure or resistant Ovarian syndrome Hypogonadotropic hypogonadism Hypothyroidism Prolactinoma Testosterone, DHEA-S, 17-Hydroxyprogesterone
  • 24.
    Ovarian Reserve Testing ovarianreserve, represents the number of oocytes available for potential fertilization at that point in time and may be assessed by serum tests or ultrasonography. 1. Age 2. AMH 3. AFC Day #3 FSH (<10 mIU/ml) and estradiol (<80 pg/ml) -Correlates with the functional status of the ovaries and the quality of the oocytes - FSH >15 only 5% success with IVF - High estradiol level increases risk of cancelling IVF cycle Ovarian reserve tests are good predictors of response to ovarian stimulation, but poor results do not necessarily predict inability to achieve a live birth.
  • 25.
    Diminished Ovarian Reserve Thepresence of decreased ovarian reserve predicts future response to ovarian stimulation Although there are no definitive criteria for diminished ovarian reserve, the following values may be considered consistent with diminished ovarian reserve: • Antimullerian hormone (AMH) value less than 1 ng/mL • antral follicle count less than 5–7 and • follicle-stimulating hormone (FSH) greater than 10 IU/L or • a history of poor response to in vitro fertilization stimulation (fewer than four oocytes at time of egg retrieval).
  • 26.
    Most common typeof Normogonadotropic normoestrogenic anovulation is PCOS. • PCOS accounts for 80 to 85% • 8% of all reproductive-aged females. • PCOS can be diagnosed using the. Rotterdam criteria for PCOS, which requires at least two of the three below listed criteria in the absence of other pathological causes. • Oligoovulation/anovulation • Clinical signs of hyperandrogenism and/or serological elevations of androgens • Polycystic ovaries demonstrated with ultrasound • PCOS is a diagnosis of exclusion PCOD
  • 27.
    Hysterosalpingography (HSG) Chlamydia AntibodyTest Assesses shape of the uterine cavity-Evaluates Tubal Less invasive and cost effective Assessment of tubal abnormalities - Tubal occlusion - Tubal irregularity - Peritubal Abnormalities HSG: Hydrosalpinx HSG: Unilateral Blocked Tube Arcuate uterus Intrauterine adhesions • Tubal spasm • Only 38% tubal blockage is confirm by laparoscopy • More specific for detecting distal tubal occlusion • Diagnostic And Therapeutic specially with oil based media. The positive predictive value and negative predictive value of HSG for assessing tubal patency have been estimated as 38% and 94%, respectively TUBAL EVALUATION
  • 28.
    Sonohysterography is thevisualization of the uterus and adnexa ultrasonographically with the infusion of fluid through a transcervical catheter Using sonohysterography, the uterine cavity usually is easily defined, and abnormalities such as endometrial polyps, submucosal fibroids, and intrauterine adhesions can be seen. More than 16% of infertile women and 40% of women with abnormal uterine bleeding will have an abnormality on sonohysterography . Sonohysterography has a sensitivity and specificity of 91% and 84%, respectively, for the detection of intrauterine structures HyCoSy (hysterosalpingo contrast sonography) - with automated 3D-coded contrast imaging technology. Laparoscopy with chromopertubation Tubal evaluation Hysterosalpingo-contrast sonography (HyCoSy)
  • 29.
    Other Tests  Hysteroscopicevaluation  To evaluate condition of uterine  Cavity (polyps, fibroids(sub-mucus), intra cavitary lesion, intra uterine adhesion( uterine synechiae), Mullerian duct anomalies(uterine septum) Endometritis  Laparoscopic evaluation  Although considered as gold standard not taken as routine investigation these days.  Check patency of fallopian tubes specially in unexplained infertility .  Tubal adhesions  To evaluate for pelvic disease,  Endometriosis (grading & Treatment)  Ovarian Pathology or uterine fibroid distorting cavity.  Mullerian anomalies
  • 30.
    INDICATION OF MRIIN FEMALE INFERTILITY • Complex adnexal masses • Endometriosis deep seated • Mullerian duct anomalies • Adenomyosis • Fibroids- Pre surgical mapping of location and vascularity of fibroid. • Intra uterine adhesion • Pyosalpinx • Cornual fibroid MRI is superior to USG in determining both tubal and peritubal component of PID. In the era of evidence based medicine. MRI has on indispensable role in diagnosis & management of female infertility Non-invasive radiation free modality
  • 31.
    • Laparoscopy forunexplained infertility • Advanced sperm function testing (eg, DNA fragmentation testing) • Postcoital testing • Thrombophilia testing • Immunologic testing • Karyotype • Endometrial biopsy • Prolactin Infertility test that should not be routinely ordered
  • 32.
    Unexplained infertility maybe diagnosed in as many as 19-20% of infertile couples the basic infertility evaluation is performed, and all the tests results are normal. At a minimum, these patients have evidence of ovulation, tubal patency, and a normal semen analysis UNEXPLAINED INFERTILITY • For most couples with unexplained infertility, the best initial therapy is a course (typically 3 or 4 cycles) of OS and IUI, either with clomiphene or letrozole, followed by IVF for those couples unsuccessful in achieving a pregnancy with OS and IUI. • There is a pressing need for additional therapies to bridge the wide gap in effectiveness between OS and IUI with oral medications and IVF. • Further research is needed into methods to improve access to care, including ART treatments.
  • 33.
    Environmental toxins affectingfertility • Pesticides • Mercury • Lead • Cadmium • Bisphenol- A • Flame retardance • Phthalates
  • 34.
    • Age • Durationof infertility • Cause of infertility • Financial resources • Sperm concentration in the sample In treatment main deciding factor are: Factors affecting modality of infertility treatment
  • 35.
    Lifestyle Changes The idealBMI for getting pregnant is between 18.5 and 24.9. Diet and Exercise • Women with extremes in body mass index (BMI) frequently present with infertility and ovulatory dysfunction. • Women with a BMI of less than 17 kg/m^2 with a history of intense exercise regimens or women with eating disorders are likely to develop hypogonadotropic hypogonadism, which causes deceased pituitary gonadotropin secretions • Women with a BMI greater than 27 kg/m^2 with anovulation can improve ovulation with weight loss alone. Multiple studies have shown that a loss of 10% of body weight will restore normal ovulation in 50 to 100% of women in less than 1 year . • Bariatric surgery Treatment / Management
  • 36.
    Infertility Period APPROACH TOTREATMENT ALGORITHM
  • 37.
    APPROACH TO TREATMENTALGORITHM Age Factor
  • 38.
    Treatment options… Overcoming Infertility Nearly90% of all infertility cases, both male and female factor, all can be treated . Treatment options are: • Expectant Treatment • Ovulation Induction & COH • Medical & Surgical treatment of Male • Laparoscopic & Hysteroscopic Surgery for Female • Intrauterine Insemination (IUI)
  • 39.
    When to attemptIUI First • At least one unblocked fallopian tube • Able to ovulate, perhaps with the help of fertility medications • Healthy ovarian reserve, good amount of healthy eggs • Normal uterine cavity • Cervical issue scarring/hostile cervix may block fertilization • Mild ovulation issue like polycystic ovarian syndrome (PCOS) • Donor sperm • Mild to moderate male factor • After male fertility preservation before cancer treatment or surgery • Same sex couple
  • 40.
    Intra-Uterine Insemination (IUI) •First line of treatment provided both or either one fallopian tubes are patent. specially in pt under age of 35 years • Simple, Non-Invasive & Cost Effective • IUI is a viable option before proceeding to ART • Processed total motile sperm(PTMS)>1 million/ml • Progressive motility >30%, morphology >4%, is the most important criteria. Sperm survival <70% • Prewash IUI semen pregnancy score (IUI-SPS)<150 • IUI+ mild COH- gives good pregnancy rate • Clinical pregnancy rate per cycle is 10-20%
  • 41.
    8 Tips forfertility wellness • Decrees stress • Solid 8 hours of sleep • Practice mindful eating • Cultivate supportive network • Balance being and doing fertile window • Regular Exercise but not excessive • Treat each day as new opportunity • Meditation (Can be done with brahma Kumari)
  • 42.
    Timely Referral ToSpecialist Care
  • 43.
    Summary • There arepotential consequences of delayed, later-age referral to a reproductive endocrinology and infertility (REI) specialist • Diagnostic tests are conducted after - 1 year of infertility for woman aged <35 years - 6 months of infertility for woman aged > 35 years • The Ob/Gy fertility specialist and patient need to work together to determine reasonable expectations and optimal treatment course • Due to new ART laws early child bearing should be promoted and fertility preservation by egg freezing should be done in case of delayed marriage and child bearing. • Diagnostic laparoscopy is no more a routine investigation for tubal testing. • Role of color doppler and 3D ultrasound is promising. • Role of MRI in fibroid, complex ovarium masses and PID is increasing. • The endpoint should be shifted from conception to live birth. • Evaluation should be done systematically which should also be cost effective to come to definite cause of infertility. 43

Editor's Notes

  • #5  It is prevalent as one in seven couples (2-9). Infertility is not just a medical problem, but many of those failing to conceive deal with medical, psychological and financial stresses related to their condition (10). More than 3 decades after the introduction of in vitro fertilization (IVF) and despite the improved success rates of assisted reproductive technologies (ART), the argument for performing laparoscopy as a part of the infertility workup still stands (11). It is agreed that the use of laparoscopy in women with decreased ovarian reserve or severe male factor infertility offers no benefit since the main treatment will remain IVF . Worldwide, infertility rates are higher in Eastern Europe, North Africa, and the Middle East. Worldwide,2% of women aged 20 to 44 were never able to have a live birth, and 11% with a previous live birth were unable to have an additional birth
  • #9  Pelvic and tubal adhesions, along with uterine and tubal abnormalities, account for a large portion of female infertility.Infectious processes within the abdomen are the leading cause of pelvic/tubal adhesions; the most common infectiousprocess to affect infertility is pelvic inflammatory disease (PID). The microorganism that carries the greatest risk ofinfertility in association with PID is Chlamydia trachomatis. One in 4 women with tubal factor infertility will havepositive antibodies to chlamydia, which are inversely proportional to pregnancy rates.[26] The number of PIDepisodes and the severity play a role in the likelihood of infertility. One study demonstrated that the pregnancy ratesfollowing PID were 89% after 1 episode, 77% after two episodes, and 46% after three episodes.[27] In terms of PIDseverity of mild, moderate, and severe, the livebirths rates were 90%, 82%, and 57%, respectively.[28]
  • #10  Hypothalamic amenorrhea or functional hypothalamic amenorrhea (FHA) is associated with eating disorders andexcessive exercise, which results in a decrease in hypothalamic GnRH secretion.[6] The decreased caloric intake,associated weight loss, or excessive exercise leads to elevated cortisol, which causes a suppression of GnRH.[7] Thedecreased or absent pulsatility of GnRH results in a decrease in the release of gonadotropins, follicle-stimulatinghormone (FSH), and luteinizing hormone (LH) from the anterior pituitary gland. These two deficiencies result inabnormal follicle growth, anovulation, and low estrogen levels.[8] The FSH and LH will have variations ranging fromnormal to low, but the hormone ratio will resemble a prepubertal female, with FSH higher than LH.[8]
  • #22 Ovulation usually occurs within 14- 26 hours of detection of urine LH surge and almost always within 48 hours. Serum estradiol attains the peak rise 24 hours prior to LH surge and about 24-36 hours prior to ovulation.
  • #27  Infertility caused by PCOS is thought to be associated with a dysfunction in developing a mature follicle leading toanovulation. The FSH and estrogen will be within normal laboratory limits. The LH can either be normal or elevated.The pathophysiology behind PCOS and infertility is not well understood; classically, abnormal pulsatility of GnRH isdescribed as a possible underlying cause. Correlating the high of arrested follicles and polycystic appearing ovaries isthe elevation of anti-Mullerian hormone (AMH).
  • #28  Hydrosalpinges, are a tubal abnormality caused by acute and chronic inflammation that damages the structuralintegrity of the fallopian. This damage leads to tubal obstruction, which blocks the distribution of physiologic fluid inthe fallopian tube and results in fluid accumulation. The belief is that hydrosalpinges impair fertility through theretrograde flow of toxins and prostaglandins into the endometrium, creating a hostile environment for implantation byimpairing endometrial receptivity.[29] The literature has demonstrated that patients undergoing in-vitro fertilizationhave a 50% decrease in pregnancy if a hydrosalpinx is present.[30]
  • #30 29
  • #35  Pelvic and tubal adhesions, along with uterine and tubal abnormalities, account for a large portion of female infertility.Infectious processes within the abdomen are the leading cause of pelvic/tubal adhesions; the most common infectiousprocess to affect infertility is pelvic inflammatory disease (PID). The microorganism that carries the greatest risk ofinfertility in association with PID is Chlamydia trachomatis. One in 4 women with tubal factor infertility will havepositive antibodies to chlamydia, which are inversely proportional to pregnancy rates.[26] The number of PIDepisodes and the severity play a role in the likelihood of infertility. One study demonstrated that the pregnancy ratesfollowing PID were 89% after 1 episode, 77% after two episodes, and 46% after three episodes.[27] In terms of PIDseverity of mild, moderate, and severe, the livebirths rates were 90%, 82%, and 57%, respectively.[28]