infertility

effect of caffeine on fertility

conflicting findings but recommendations of caffeine intake moderation in infertile women seem prudent - https://t.me/ProjectTGM/1943

Hormonal testing in the male

- analogous to endocrine testing in an anovulatory female - Most urologists will defer testing unless a sperm concentration is below 10 million/mL. - FSH, LH, PRL, T levels - low FSH and T in hypothalamic dysfunction, such as IHH or Kallmann syndrome: gonadotropin treatment - high FSH and low T in testicular dysfunction and most men with oligospermia are in this category: treatment?

The infertility evaluation can be conceptually simplified into confirmation of

(1) ovulation, (2) normal female reproductive tract anatomy, and (3) normal semen characteristics https://t.me/ProjectTGM/1955

Klinefelter syndrome

- 1 in 500 men in the general population - accounts for 1-2% of male infertility cases - classically, these men are tall, undervirilized, and have gynecomastia and small, firm testes

fecundability is highly age-related

- A significant decrease begins at approximately age 32 years, and a more rapid decline follows after age 37. - This decline in conception rates is associated with a rise in poor pregnancy outcome rates, primarily due to higher aneuploidy rates. - most experts agree that evaluation is considered after only 6 months in women older than 35 years https://t.me/ProjectTGM/1956

antral follicle count (AFC) as an ovarian reserve predictor

- AFC is commonly used as a reliable predictor for subsequent response to ovulation induction - The number of small antral follicles reflects the size of the resting follicular pool - Antral follicles between 2 and 100mm are counted in both ovaries. - The total AFC usually ranges between 10 and 20 in a reproductive-aged woman. - An AFC with <3 to 6 total antral follicles predicts poor response to gonadotropin stimulation during IVF cycles, but this measure is limited by low sensitivity

antimullerian hormone (AMH) as an ovarian reserve predictor

- AMH is expressed by the fetal testes during male differentiation to prevent development of the mullerian system (fallopian tubes, uterus, and upper vagina) - AMH is also expressed by the granulosa cells of small preantral follicles but has limited expression in larger follicles. This suggests that AMH plays a role in dominant follicle recruitment - advantages AMH compared with FSH and inhibin testing? - under consideration as a tool for diagnosis of PCOS

midluteal serum PRO

- Adequate progesterone levels are required for endometrial preparation prior to implantation. Inadequate endometrial development due to suboptimal progesterone production leads to LPD - In a classic 28-day cycle, serum is obtained on cycle day number 21 following the first day of menstrual bleeding, or 7 days following ovulation. - Levels during the follicular phase are generally <2 ng/mL, - Values above 4-6 ng/mL correlate with ovulation and progesterone production by the corpus luteum - PRo is secreted as pulses: so single measurement is not enough - no acceptable threshold is set but some use 10ng/dL (although unproved and costly) - the midluteal PRO level is best regarded as an acceptable test for ovulation but not an absolute indicator of adequate luteal function

DNA fragmentation

- Although some degree of DNA damage is likely repaired during embryogenesis, the location and extent of damage may lower fertilization and raise miscarriage rates - Greater levels of DNA damage are associated with advanced paternal age and external factors such as cigarette smoking, chemotherapy, radiation, environmental toxins, varicocele, and genital tract infections - samples with abnormal DNA fragmentation rates, higher levels of reactive oxygen species are observed and antioxidants vitamin C and vitamin E supplementation has been proposed even though data are lacking - tests to analyze for DNA integrity: a. Sperm Chromatin Structure Assay(SCSA) b. terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay c. single-cell gel electrophoresis assay (COMET) d. sperm chromatin dispersion test (SCD) - these tests are semiqualitative, no consensus on threshold values and their ability to predict successful pregnancy, and not routinely recommended

uterine abnormalities

- Common congenital anomalies include uterine septum, bicornuate uterus, unicornuate uterus, and uterine didelphys. - Acquired anomalies include intrauterine leiomyomas, adenomyosis, polyps, and Asherman syndrome.

genetic screening in the female

- For all women considering pregnancy, current recommendations support offering carrier screening for cystic fibrosis, spinal muscular atrophy, thalassemias, and hemoglobinopathies. - Additionally, sickle cell screening in African Americans and multiple disorders in the Ashkenazi Jewish - with POI, karyotype testing for trisomy 21 mosaicism and Fragile X premutation carrier screening

genetic screening in the male

- Genetic abnormalities are a relatively common cause of abnormal semen characteristics - WHO recommendations: karyotype testing should be performed for any male with a. severe oligospermia (<5 X 106 sperm/mL) or b. nonobstructive azoospermia - 15% of azoospermic men and 5% of severely oligospermic men will have an abnormal karyotype - Klinefelter syndrome (47,XXY) - testing for microdeletion of the Y chromosome is offered for men with severely low sperm counts and a normal karyotype - CBAVD - In excess of 1000 genes are believed to be required for successful sperm development. Mutations in more than 30 of these genes cause of male infertility

infertility: subdivision

1. primary infertility, that is, no prior pregnancies, and 2. secondary infertility, referring to infertility following at least one prior conception medbullets Inability to conceive - after 1 year of unprotected sex in the absence of any known causes of infertility - after 6 months if the woman is > 35 years of age or in couples with known risk factors for infertility

SIS

- Infusion of saline into the endometrial cavity during sonography performed in the follicular phase provides another approach to create contrast between the cavity and uterine walls. - This procedure has many names including hysterosonography, sonohysterography, or saline infusion sonography (SIS) - sensitivity of 75% and specificity of more than 90% for detecting endometrial defects. - PPV of 50% and NPV of 95% (greatly exceeds NPV of HSG) - SIS can help determine what portion of a submucous leiomyoma is within the cavity: only those with less than a 50% intramural component are considered for hysteroscopic resection - does not provide information regarding the fallopian tubes, although rapid loss of saline into the pelvis is certainly consistent with at least unilateral patency - SIS is generally less painful than HSG and does not require radiation exposure. https://t.me/ProjectTGM/1642

bariatric surgery and infertility

- Similar to women, rigorous data describing the effects of bariatric surgery on male reproductive health are lacking

semen analysis terminology

- Oligospermia: sperm concentration 10-15 million sperm/ml (mild-moderate) or <5-1 0 million/ml (severe) - Asthenospermia: greater proportion of immotile spermor sperm with decreased motility - Teratospermia or teratozoospermia: Increased proportion of morphologically abnormal sperm - Azoospermia: semen present but lacks sperm - Aspermia: sperm and seminal plasma lacking (anejaculation) - Leukocytospermia: Increased WBC count - Necrospermia: all sperm nonviable or immotile

evaluation for ovarian reserve

- Ovulatory status does not provide a complete picture of ovarian function. - cause of DOR: most often result of advancing age, but also due to smoking, genetic conditions, or prior ovarian surgery, chemotherapy, or pelvic irradiation - tests to assess ovarian reserve lack sensitivity and PPV for DOR - these tests are more accurate as predictors of ovarian response to pharmacologic stimulation than as predictors of subsequent pregnancy - Currently, early follicular measurement of FSH is probably the most cost-effective approach for the general practitioner - serum AMH level - Measuring serum inhibin B levels and the clomiphene citrate challenge test have fallen out of favor - estradiol - antral follicle count (AFC) - a normal test result does not negate the effect of a woman's age on her fertility status

capacitation

- To fertilize an oocyte, human sperm must undergo capacitation - Capacitation results in sperm hyperactivation and the ability to release acrosomal contents, which allow penetration of the ovum's zona pellucida.

ovaries vs testes

- Unlike the ovary, testes contain stem cells that allow ongoing production of mature germ cells throughout a male's life. - Analogous to the ovary, testes have two functions: the generation of mature germ cells (sperm) and the production of male hormones, primarily T - In simplistic terms, Leydig cells are similar to the theca cells of the ovary

testicular volume

- a normal volume is between 15-25 mL - Most of this volume is provided by the seminiferous tubules. - Thus, a small testicular volume is a strong indicator of abnormal spermatogenesis. - Small testes are unlikely to produce normal sperm numbers.

male infertility evaluation methods

1. sperm testing methods - sperm analysis - DNA fragmentation - antisperm antibodies - tests for sperm function: mannose fluorescence assay, hemizona assay, sperm penetration assay, and acrosome reaction test. Most are no longer used and are not considered part of a basic infertility evaluation 2. hormonal evaluation 3. Scrotal and transrectal sonography, and MRI 4. testicular biopsy 5. genetic screening

PE: female

- VS, Wt, Ht - short stature may reflect a genetic condition such as Turner syndrome - Hirsutism, alopecia, or acne indicates the need to measure androgen levels. - Acanthosis nigricans is consistent with insulin resistance associated with PCOS or diabetes or, much less commonly, Cushing syndrome. - Galactorrhea is often indicative of hyperprolactinemia. - thyroid abnormalities - inability to place a speculum may raise doubts about coital frequency - moist and rugated vagina and adequate cervical mucus: both indicate adequate EST production - An enlarged or irregularly shaped uterus may reflect leiomyomas, whereas a fixed uterus suggests pelvic scarring due to endometriosis or prior pelvic infection. - Uterosacral nodularity or ovarian masses may additionally implicate endometriosis or, less commonly, malignancy. - cervical ca screening, breast exam - when indicated by age or family history, a mammogram is obtained prior to initiating hormonal treatment.

evaluation for ovulation

- acquired or inherited abnormalities within the hypothalamus, anterior pituitary, or ovaries - hypothalamus: acquired (due to lifestyle like excessive exercise, eating disorders, or stress) or inherited (dysfunction or improper migration of the hypothalamic GnRH neurons as in IHH or Kallmann syndrome) - Thyroid disease and hyperprolactinemia. 1. clinical evaluation: menstrual cycle, BBT, ovulation predictor kits 2. evaluation for ovarian reserve: FSH, AMH, inhibin B, clomiphene citrate challenge,

chromotubation

- a dilute dye is injected through an acorn cannula placed against the cervix or through a balloon catheter positioned within the uterine cavity - tubal spill is evaluated through the laparoscope - 1mL of methylene blue is mixed with 50-100 mL of sterile saline - methylene blue rarely may induce acute methemoglobinemia. particularly in patients with G6PD deficiency

antisperm antibody assay

- antisperm antibodies detected in as many as 10% of men - their negative fertility effect is controversial - particularly prevalent following vasectomy, testicular torsion, epididymitis, testicular biopsy, or other clinical situations in which the blood-testis barrier is breached - Treatment historically included corticosteroids a. their efficacy to improve fertility is unclear b. significant side effects can include aseptic necrosis of the hip - antisperm antibody assay does not need to be a routine component of an infertility evaluation

spermatogenesis and factors affecting it

- begins with a diploid (46,XY) spermatogonial cell and results in four mature sperm with a haploid (23,X or 23,Y) karyotype - most sperm cytoplasm is lost, mitochondria are positioned in the sperm midpiece, and sperm flagella develop - high T levels are integral to normal spermatogenesis - LH stimulates production of T by the Leydig cells - FSH increases LH receptor density on the Leydig cells, thus indirectly contributing to T production - FSH also elevates production of SHBG, also called androgen-binding protein which binds T and maintains high concentrations of this hormone in the seminiferous tubules - testicular volume also often reflects spermatogenesis - genes on the Y chromosome and autosomal genes affect spermatogenesis - male age: how?

serial ovarian sonographic evaluations (for ovulation)

- can demonstrate the development of a mature antral follicle and its subsequent collapse during ovulation - time consuming, and ovulation can be missed - excellent for supporting the diagnosis of PCOS

mechanisms of infertility in endometriosis (5)

- chronic inflammation and intraperitoneal bleeding can lead to pelvic adhesions - an increase in peritoneal fluid inflammatory factors, - alterations in endometrial immunologic function, - poor oocyte or embryonic quality, or - impaired implantation

seminiferous tubules

- contain developing sperm and support cells called Sertoli cells (or sustentacular cells) - Sertoli cells form tight junctions that produce a blood-testis barrier: avascular space within the seminiferous tubules a. protects sperm from antibodies and toxins b. also makes these cells dependent on diffusion for oxygen, nutrients, and metabolic precursors - Leydig cells (or interstitial cells) are located between the seminiferous tubules and are responsible for steroid hormone production - In simplistic terms, Leydig cells are similar to the theca cells of the ovary

causes of abnormalities in mucus quantity and quality

- cryosurgery, cervical conization, o rLEEP can affect production - Cervical infection may also worsen mucus quality, but data are conflicting

tubal and pelvic factors

- etiologies for pelvic adhesions include tubal disease, especially pelvic infection; endometriosis; and prior pelvic surgery - adhesions can prevent normal tubal movement, ovum pick-up, and transport of the fertilized egg into the uterus. - in developed countries: tubal disease in 1/3 to 1/4th of infertile women - in US: the MCC of tubal disease is infection with C trachomatis or N gonorhoeae - in developing countries, genital TB may account for 3-5% of infertility cases - mechanisms of infertility in endometriosis (5) - Salpingitis isthmica nodosa - prior ectopic pregnancy, even if treated with MTX, implies the likelihood of significant tubal damage - pelvic inflammation, due to blood, infection, or irritation caused by mature cystic teratoma (dermoid) contents

HSG

- excellent predictor of tubal patency but is less effective at predicting normal tubal function or pelvic adhesions - although loculations of dye around the tubes may be suggestive of peritubal or pelvic adhesions - pregnancy rates can rise after HSG Why? - HSG is a valuable tool for initial uterine cavity evaluation a. polyp, leiomyoma, or adhesion within the cavity will block dye diffusion and create an intrauterine "defect" b. FPR from blood clots, mucus plugs, or shearing of the endometrium during placement of the intrauterine catheter - 98% sensitive and 35% specific and have a PPV of 70% and NPV of 8%. HSG can also define developmental uterine anomalies - Y-shaped uterus may be either a uterine septum or bicornuate uterus a. With a uterine septum, a smooth fundal contour is found, b. with a bicornuate uterus, a cleft between the two uterine horns is seen. This is an important distinction, as a septum is often resected, but a bicornuate uterus is usually not treated.

fecundability vs fecundity

- fecundability is the ability to conceive - fecundability is highly age-related -

retrograde ejaculation

- follows failed closure of the bladder neck during ejaculation and allows seminal fluid to flow backward into the bladder - suspected in men with DM, spinal cord damage, prior prostate or other retroperitoneal surgery that may have damaged nerves, or beta blocker use - A postejaculatory urinalysis can detect sperm in the bladder and confirm the diagnosis. - If urine is properly alkalinized, these sperm are viable and can be retrieved to achieve pregnancy

effects of alcohol on fertility

- heavy alcohol intake lowers fertility in women and has been associated with a decline in sperm counts and greater sexual dysfunction in men - 5-8 drinks per week negatively affects female fertility - alcohol is also detrimental to early pregnancy

luteal phase endometrial biopsy

- hoped to reflect both corpus luteum function and endometrial response but it's utility is severely hampered by high intraobserver and interobserver variability during histologic evaluation - An out-of-phase biopsy is found nearly as frequently in fertile as in infertile women - in its current form, EMB is no longer considered a routine pan of infertility evaluation - Potential markers for uterine receptivity include osteopontin, cytokines, cell adhesion molecules, ion channels, and the L-selectin ligand, which has been proposed to mediate embryo attachment

genital TB: incidence, pathogenesis and prognosis

- in developing countries, genital TB may account for 3-5% of infertility cases - tubal damage and endometrial adhesions are underlying causes - Genital TB typically follows hematogenous seeding of the reproductive tract from an extragenital primary infection. - The likelihood of a return to fertility after antitubercular treatment is low, and IVF with embryo transfer remains the most reliable approach.

medications are known to worsen semen parameters

- including cimetidine, erythromycin, gentamicin, tetracycline, and spironolactone - Moreover, cigarettes, alcohol, illicit drugs, and environmental toxins all adversely affect semen quality - The rising use of anabolic steroids also decreases sperm production by suppressing the output of intratesticular testosterone - Although the effects of many medications are reversible, anabolic steroid abuse may lead to lasting or even permanent damage to testicular function

myoma: pregnancy complications and management

- infertility - miscarriage, placental abruption, and preterm labor are potential problems - no algorithm incorporating tumor number, volume, or location accurately predicts the need to remove them, either to improve implantation rates or to lower pregnancy complications - nevertheless, experts suggest/consider myomectomy in a. removal of submucosal fibroids that significantly distort the endometrial cavity b. leiomyomas larger than 4-5cm or multiple smaller tumors in this range regardless of location - surgical benefits are weighed against postoperative complications like adhesions, Asherman syndrome and need for CD

Salpingitis isthmica nodosa

- inflammatory condition of the fallopian tube, characterized by nodular thickening of its isthmic portion - smooth muscle proliferation and diverticula of tubal epithelium contribute to this thickening - typically develops bilaterally and progressively leads to ultimate tubal occlusion and infertility

clinical evaluation for ovulation

- menstrual history is an excellent predictor of regular ovulation - A woman with cyclic menses at an interval of 25 to 35 days and duration of bleeding of 3 to 7 days is most likely ovulating. - each woman will have her own normal pattern - Probable ovulation is also suggested by mittelschmerz, moliminal symptoms, and dysmenorrhea (although severe dysmenorrhea may suggest endometriosis) - BBT: A postovulatory rise in progesterone levels increases basal temperature by approximately 0.4 to 0.8 o F - ovulation predictor kits - serum PRO - endometrial biopsy - US

T replacement in men with high FSH and low T

- normal spermatogenesis requires high levels of intratesticular T, which cannot be achieved with exogenous T - plus, many of these men will lack spermatogonial stem cells - Thus, T replacement will not rescue sperm production. - In fact, replacement will decrease gonadotropin stimulation of remaining testicular function through negative feedback - but replacement will provide other benefits such as improved libido and sexual function, maintenance of muscle mass and bone density, and a general sense of well-being

effect of EST on cervical mucus

- normally thick and impervious to sperm and ascending infections - high EST levels at midcycle induce mucus to become thin and stretchy and to have a higher NaCl concentration a. filters out nonsperm components of semen and forms channels that help direct sperm into the uterus b. creates a reservoir for sperm allowing ongoing release during the next 24-72 hrs and extends the potential time for fertilization - moist and rugated vagina and adequate cervical mucus: both indicate adequate EST production

testing for microdeletion of the Y chromosome

- offered for men with severely low sperm counts and a normal karyotype - Up to 15% of men with severe oligospermia or azoospermia will have small deletions in a region of the Y chromosome termed the azoospermia factor region (AZF) - deletion is within the AZFa or AZFb subregions, it is unlikely that viable sperm can be recovered for use in IVF - Most men with an AZFc deletion will have viable sperm at biopsy. - AZFd region: these patients have apparently normal spermatogenesis

TVS

- particularly helpful during the luteal phase, when the thickened endometrium acts as contrast to the myometrium - improved with 3D imaging and saline infusion -

functions of AMH

- prevent development of the mullerian system in fetus - a role in dominant follicle recruitment

Female age and fertility have a clear inverse relationship

- primarily attributable to a decline in oocyte quality and quantity - accumulating risk for the development of medical disorders or uterine and pelvic abnormalities also contributes - Ongoing atresia of nondominant follicles proceeds throughout a woman's reproductive life span. - Also, the risks of genetic abnormalities and mitochondrial deletions in the remaining oocytes substantially rise as a woman ages - The overall miscarriage risk in women older than 40 years is estimated to be 50 to 75% - The follicular loss rate and age at menopause varies between women and is likely genetically determined. https://t.me/ProjectTGM/1956

Male History

- pubertal development and sexual function difficulties - ED, particularly in conjunction with diminished beard growth. may suggest lower T levels - ejaculatory problems - hypospadias could result in suboptimal semen deposition - STDs and GU infections including epididymitis or prostatitis, may lead to vas deferens inflammation and obstruction - mumps can create testicular inflammation and damage spermatogenic stem cells - cryptorchidism, testicular torsion, or testicular trauma may suggest abnormal spermatogenesis - varicoceles (how?) - heat? - prior chemotherapy or local radiation treatment that may damage spermatogonial stemcells - HTN, DM, and neurologic disorders can be associated with erectile dysfunction or retrograde ejaculation - obesity-related secondary hypogonadism,erectile dysfunction, and infertility - meds (like what?), alcohol, cigarette, illicit drugs, steroids - exercise

semen: collection, content

- refrain from ejaculation for 2-3 days - masturbate into a sterile cup or specially designed Silastic condoms without lubricants and sample should arrive in an hour - liquefaction, or thinning of the seminal fluid, due to enzymes from the liquid contribution of the prostate gland: takes 5-20 minutes and allows more accurate evaluation of the sperm - Ideally, two semen samples separated by at least a month are analyzed - 80% of semen volume comes from the seminal vesicles - seminal fluid is alkaline to protect sperm from acidity in prostatic secretions and in the vagina - fructose as an energy source for sperm - seminal analysis - endocrine and genetic evaluation is indicated for men with abnormal sperm counts

imaging and testicular biopsy in male infertility

- scrotal US to examine testicular morphology and identify varicocele or epididymal cysts or abscesses - transrectal US to examine prostate and seminal vesicles or more central areas of obstruction in the vas deferens - MRI for imaging male accessory sex glands and ducts - open or percutaneous testicular biopsy in a severely oligospermic or azoospermic male to determine whether viable sperm are present in the seminiferous tubules - to obtain sperm for use in intracytoplasmic sperm injection or biopsy specimen can be cryopreserved for future extraction of sperm during an IVF cycle - Thus, the biopsy may have diagnostic, prognostic, and therapeutic value

PE: male

- secondary sexual characteristics that reflect androgen production such as beard growth, axillary and pubic hair, and perhaps male pattern balding should be present. - Gynecomastia or eunuchoid habitus may suggest Klinefelter syndrome - penile urethra should be at the glans tip for proper semen deposition in the vagina - testicules, epididymis, prostate exam: what are the findings? - Testicular length measures at least 4cm and a minimal testicular volume is 20ml - A testicular mass may indicate testicular cancer, which can present as infertility. - The epididymis should be soft and nontender to exclude chronic infection. - Epididymal fullness may suggest vas deferens obstruction. - The prostate should be smooth, nontender, and normal size- - the pampiniform plexus of veins is palpated for varicocele. - both vasa deferentia should be palpable - Congenital bilateral absence of the vas deferens is associated with mutation in the gene responsible for cystic fibrosis

semen analysis interpretation

- semen volume, pH, and presence or absence of fructose - An acidic pH or lack of fructose is consistent with obstruction of the efferent ductal system - Low semen volume may indicate incomplete collection, short abstinence interval, partial vas deferens obstruction or retrograde ejaculation - Partial or complete vas deferens obstruction may be caused by infection, tumor, prior testicular or inguinal surgery, or trauma - rapid (grade 3 to 4}, slow (grade 2}, and nonprogressive (grade 0 to 1) movement - Total progressive motility is the percentage of sperm exhibiting forward movement (grades 2 to 4) - hypoosmotic swelling test - Significantly lower fertilization rates are seen when normal morphology of the sample falls below 4% https://t.me/ProjectTGM/1968

In general, infertility evaluation is offered to any couple that has failed to conceive in 1 year.

- several scenarios may prompt earlier intervention, for example, an anovulatory woman or a woman with a history of severe PID - most experts agree that evaluation is considered after only 6 months in women older than 35 years

At least 15 percent of reproductive-aged men and women in the United States smoke cigarettes.

- smoking's negative effects on female fecundity do not appear to be overcome by ART - toxins in the smoke can accelerate follicular depletion and increase genetic mutations in gametes or early embryos - linked to higher rates of miscarriage, abruption, fetal-growth restriction, and preterm labor - vasoconstrictive and antimetabolic properties of some cigarette smoke components such as nicotine, CO2, and cyanide may lead to placental insufficiency - although male smokers often have comparatively reduced sperm concentrations and motility, these often remain within the normal range.

ovulation predictor kits

- these kits measure urinary LH concentration by colorimetric assay - widely available and relatively easy to use - In general, a woman begins testing 2-3 days prior to the predicted LH surge, and testing is continued daily. - No clear consensus guides the optimal time of day to test. Because the LH surge spans 48-50 hours, timing is probably not critical as long as the test is performed daily. - In most instances, ovulation will occur the day following the urinary LH peak - equivocal results can be repeated in 12hrs - 100% sensitivity and 96% accuracy: undoubtedly an overestimate of typical-useresults

effects of marijuana on fertility

- time to pregnancy was not lengthened by marijuana use in either men or women - neonates born to exposed mothers had a higher risk of premature rupture of membranes, prematurity, and intrauterine fetal demise

evaluation for female anatomic abnormalities

- tubal and pelvic factors - uterine abnormalities - anatomy evaluation: HSG, TVS, 3D TVS, SIS, hysteroscopy, laparoscopy, MRI - cervical abnormalities

percentage of couples achieving pregnancy vs time (months)

1 mo.: 20-36% 3 mos.: 57% 6 mos.: 72% 12 mos.: 85% 24 mos.: 93%

advantages AMH compared with FSH and inhibin testing

1. AMH expression is gonadotropin-independent and therefore is relatively independent of cycle stage and is consistent across cycles. 2. AMH levels correlate with ovarian primordial follicle number more strongly than FSH or inhibin levels 3. AMH levels may drop prior to observable changes in FSH or estradiol levels, thereby providing an earlier marker of waning ovarian function 4. a steady decline in AMH serum levels across the reproductive life span: 3ng/mL at 25, 1ng/mL at 35-37 yrs 5. reference levels for FSH, estradiol, and AMH can vary between laboratories

Eunuchoid habitus

A body habitus that is tall, slim and underweight, with long legs and long arms (i.e., arm span exceeds height by 5 cm or more). https://t.me/ProjectTGM/1953

varicoceles: definition, pathophysiology, incidence and management

A varicocele consists of dilated veins of the pampiniform plexus of the spermatic cords that drain the testes. - Varicoceles are believed to raise scrotal tern~perature, however, the negative effects of varicoceles on fertility are controversial - Although 30-40% of men seen in infertility clinics are diagnosed with a varicocele, nearly 20% of men in the general population are similarly affected. - Current guidelines recommend against surgical repair of a nonpalpable, that is, subclinical varicocele for infertility. However, treatment of pain or other symptoms may be warranted

Ovulatory status does not provide a complete picture of ovarian function.

A woman may have regular, ovulatory menses but have reduced follicular response to ovarian stimulation compared with other women of similar age due to a smaller ovarian follicle pool. In this situation, the woman is said to have decreased or diminished ovarian reserve (DOR) and, in more severe presentations, primary ovarian insufficiency (POI).

AMH levels are under consideration as a tool for diagnosis of PCOS.

AMH raised two- to threefold in affected women compared with normal cycling women - consistent with the multiple early follicles found in patients with PCOS

testes have two functions

Analogous to the ovary, testes have two functions: - the generation of mature germ cells (sperm) and - the production of male hormones, primarily T

In general, uterine anomalies do not cause infertility but may be associated with miscarriage, malpresentation, or preterm birth.

Accordingly, it may be reasonable to surgically treat a uterine anomaly to improve pregnancy outcome - However, a couple is carefully counseled that the conception rate itself is unlikely to be affected.

Compared with fertile males, males with unilateral or bilateral cryptorchidism have fertility rates of 80% and 50%, respectively

Although unclear, the relatively warm intraabdominal temperature may cause permanent stem cell damage. Alternatively, genetic abnormalities that led to the abnormal testis location may also affect sperm production (W, 4th )

A social history focuses on lifestyle factors such as eating habits. Of these, abnormalities in GnRH and gonadotropin secretion are clearly related to BMI >25 or <17.

An estimated 40 percent of women are obese, and most agree this incidence is rising. In these women, infertility is primarily related to a higher incidence of ovulatory dysfunction, but data also suggest that fecundity may be lowered by poorer oocyte quality and altered endometrial function. - Although difficult to achieve, even modest weight reduction in overweight women is correlated with normalized menstrual cycles and subsequent pregnancies. - BMI > 25 kg/m2 or < 17 kg/m2. note, both extremes have been associated with infertility (medbullets)

BBT: evaluation, pathophysiology, interpretation, disadvantages

Basal body temperature (BBT) - woman's morning oral temperature be graphically charted - Oral temperatures are usually 97.0 to 98.0 o F during the follicular phase. - A postovulatory rise in progesterone levels increases basal temperature by approximately 0.4 to 0.8 o F - This biphasic temperature pattern is strongly predictive of ovulation - although inexpensive test, it is insensitive in many women - the temperature rise follows ovulation, and therefore the window of maximal fertility has been missed

Although total motile sperm count correlates with fertility, not all males with "normal" semen parameters display normal fertility

Conversely, patients with semen analysis results outside the reference range may achieve pregnancy. - The lack of absolute predictive value for this test is likely due to the fact that it does not provide information regarding sperm function, that is, the ultimate ability to fertilize an oocyte.

hysteroscopy

Endoscopic evaluation of w intrauterine cavity is the preferred method to define intrauterine abnormalities. - concurrently diagnose and treat abnormalities

laparoscopy

Direct inspection provides the most accurate assessment of pelvic pathology, and laparoscopy is the gold standard approach. - Chromotubation may be performed - Laparoscopy allows both diagnosis and immediate surgical treatment of abnormalities such as endometriosis or pelvic adhesions - invasive; not advocated in place of HSG as part of the initial infertility evaluation except in suspected a. endometriosis or b. prior pelvic inflammation - hysteroscopy can be added - in operative hysteroscopic cases, laparoscopy can help direct surgery and avoid perforation, for example, during septal incision

prevalence of endometrial polyps in infertile women

Endometrial polyps are found in an estimated 3-5 percent of infertile women - The prevalence is higher in women with symptoms such as intermenstrual or postcoital bleeding.

FSH and estradiol as an ovarian reserve predictor

FSH - "cycle day 3" FSH: may reasonably be drawn between days 2 and 4 following menses onset. - With declining ovarian function, the support cells (granulosa cells and luteal cells) secrete less inhibin and FSH levels rise in the early follicular phase - A value>10 miUImL may indicate significant loss of ovarian reserve and prompt more complete evaluation EST - paradoxically, despite the overall depletion of ovarian follicles, EST levels in older women are elevated early in the cycle due to greater stimulation of ovarian steroidogenesis by elevated FSH levels - A cycle-day-3 estradiol level >80 pg/mL is considered abnormal - paired FSH and estradiol measurement is no longer recommended for ovarian reserve evaluation because estradiol provides limited additional information compared with FSH testing alone

Infertile women seeking treatment should have serum TSH measured before treatment is started and every 2 weeks after the initiation of treatment because the risk of developing hypothyroidism is significant. Furthermore, the early diagnosis of hypothyroidism and prompt L-thyroxine therapy may improve pregnancy outcome

G, 8th on Hypothyroidism, pp: 938 - it appears reasonable, in an infertility workup, to determine serum TgAb in the presence of a negative serum TPOAb (https://t.me/ProjectTGM/2431)

Spinnbarkeit

German for spinnability - Spinnbarkeit is a property of viscoelastic fluids that describes their capacity to be drawn out into an unbroken strand. - Synonymous terms include spinnability and fibrosity. - Human bodily fluids that can exhibit a degree of spinnbarkeit include mucus (especially cervical mucus), saliva and synovial fluid https://radiopaedia.org/articles/spinnbarkeit

Female History

Gynecologic - menstruation characteristics, prior contraceptive use, coital frequency, possible menopause symptoms, and infertility duration - previous endometriosis, recurrent ovarian cysts, leiomyomas, STDs, or PID - prolonged time to conception may suggest borderline fertility and may raise the chance of determining an etiology - miscarriage, preterm delivery, retained placenta, postpartum D&C, chorioamnionitis, or fetal anomalies - coital history, including frequency and timing of intercourse - dyspareunia may point to endometriosis. Medical and Surgical - symptoms of hyperprolactinemia or thyroid disease - symptoms of androgen excess such as acne or hirsutism may point to PCOS or, much less commonly, CAH - prior chemotherapy or pelvic irradiation may suggest ovarian failure - ensure that all indicated vaccinations are current - medications like NSAIDs may adversely affect ovulation - herbal remedies are mostly discouraged - folate supplementations - Previous abdominal surgeries, especially if linked to endometriosis or adhesion formation, can lower fertility. - cervical conization can diminish cervical mucus and cervical competence - uterine surgery can predispose to intrauterine adhesions with resultant infertility. Social - eating habits and BMI - cigarette smoking lowers fertility rates - alcohol - caffeine - illicit drugs. Environmental Factors - endocrine-disrupting chemicals (EDCs). Ethnicity and Family History - family history of infertility, recurrent miscarriage, or fetal anomalies may point to a genetic etiology - both PCOS and endometriosis OCXW' in familial clusters.

Several approaches for evaluating pelvic anatomy are (5)

HSG, TVS, 3D TVS, SIS, hysteroscopy, laparoscopy, MRI

infertility: incidence

Infertility is common and affects 10-1 5% of reproductive-aged couples - Of note, even without treatment, approximately half of women will conceive in the second year of attempting. - 10-15% in US, more common in developing countries (medbullets)

Genetic testing before conception is often more straightforward and less stressful for the couple than delaying until pregnancy has been achieved.

Knowing the risk of having an affected child, a couple may consider preimplantation genetic diagnosis, prenatal genetic testing, or the use of donor gametes.

leiomyomas may diminish fertility by

Leiomyomas may diminish fertility by proposed mechanisms that include - endometrial cavity distortion with associated changes in blood flow and - endometrial maturation; - endometrial inflammation; - disordered uterine contractility that may hinder sperm or embryo transport; - obstruction of the proximal fallopian tubes; or - interreference with ovum capture

effect of male age on spermatogenesis

Male fertility likely diminishes modestly with aging. - across age, sperm concentration is maintained, however, sperm motility and morphology progressively worsen - the higher incidence of erectile and other sexual dysfunction with male aging - although advancing male age may lower fertility, it is probably insignificant compared with aging changes in women - Greater levels of DNA damage are associated with advanced paternal age and external factors such as cigarette smoking, chemotherapy, radiation, environmental toxins, varicocele, and genital tract infections.

Admittedly, current data do not prove causation, but only correlation, between smoking and infertility or adverse pregnancy outcomes.

Nevertheless, smoking is discouraged for both male and female partners planning pregnancy.

accumulating data suggest that fertility status may be a marker of overall health in both men and women

Phrased differently, the causes of infertility may be physiologically or genetically linked to somatic disorders either through association or by common pathophysiologic mechanisms. As a result, the infertility evaluation may allow early detection, prevention, and intervention for serious chronic diseases.

Successful pregnancy requires a complex sequence that includes ovulation, ovum pick-up by a fallopian tube, fertilization, transport of a fertilized ovum into the uterus, and implantation into a receptive uterine cavity. With male infertility, sperm of adequate number and quality must be deposited at the cervix near the time of ovulation.

Remembering these critical events can aid a logical evaluation and treatment strategy.

Although the evidence quality is generally low, bicycling has been associated with erectile dysfunction and decreased sperm concentration.

Similar effects are suggested in long distance runners.

the location of the testes is outside of the pelvis: why tho?

Spermatogenesis is optimal at temperatures slightly below body temperature, hence the location of the testes outside of the pelvis. - Illness with high fevers or chronic hot tub use can temporarily impair sperm quality. But, no definitive evidence supports boxer under wear as advantageous

a fertile window

The chance of conception is increased from the 5 days preceding ovulation through the day of ovulation

Poor semen quality has been associated with higher rates of diabetes, ischemic heart disease, and mortality and an increased individual and familial cancer risk.

These findings suggest semen quality may be a biomarker of overall health

semen analysis results, particularly morphologic interpretation, may differ between laboratories

Thus, reference ranges for the laboratory being used should be known.

Adenomyosis is thought to impact fertility and obstetric outcomes via functional and structural defects in the endometrium and myometrium

W, 4th

Although sperm concentrations will drop with greater coital frequency, this decline is generally too small to significantly lower the chance of fertilization

W, 4th

In a fertile male, approximately 100 to 200 million sperm are produced each day

W, 4th

In general, infertility can be attributed to the female partner one third of the time, the male partner one third of the time, and both partners in the remaining one third.

W, 4th

Most couples are more correctly considered to be subfertile, rather than infertile, as they will ultimately conceive if given enough time. (W, 4th)

W, 4th

risk of tubal infertility in PID

With PID, tubal infertility has been estimated to follow in 12%, 23%, and 54% of women following one, two, or three cases of PID, respectively - Nevertheless, an absent PID history is not overly reassuring, as nearly one half of patients who have tubal damage have no clinical history of antecedent disease

inhibin

a peptide hormone that is responsible for inhibiting FSH secretion by the anterior pituitary gonadotropes

postcoital test

aka the Sims-Huhner test - A couple is requested to have intercourse on the day of ovulation, and a sample of the cervical mucus is evaluated for elasticity (Spinnbarktit} and for the number of motile sperm per HPF - limited consensus on the definition of a normal test - also, a normal postcoital test did not predict greater cumulative pregnancy rates - will provide basic information regarding mucus production, appropriate intercourse practices, and presence of motile sperm

Ovulatory cycles are more likely to be associated with dysmenorrhea, although

although severe dysmenorrhea may suggest endometriosis

A standardized alcoholic drink is typically defined as ___

as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of hard alcohol. - 354.882ml, 147.868ml, 44.3603ml, respectively

CBAVD

congenital bilateral absence of the vas deferens - obstructive azoospermia may be due to CBAVD - 70-85% of men with CBAVD will have mutations found in the cystic fibrosis transmembrane conductance regulator gene(CFTR gene), although not all will have clinical cystic fibrosis - essentially all men with clinical cystic fibrosis will have CBAVD . Fortunately, testicular function in these men is usually normal, and adequate sperm may be obtained by epididymal aspiration to achieve pregnancy through IVF

leukocytospermia: definition and management

defined as greater than 1 million WBCs per ml - Round cells maybe either leukocytes or immature sperm: WBCs can be distinguished from immature sperm using various techniques, including a myeloperoxidase stain for WBCs - leukocytospermia may indicate chronic epididymitis or prostatitis a. empiric antibiotic treatment prior to obtaining a repeat semen analysis: doxycycline 100mg PO BID for 2 wks, or b. culture of any expressible discharge or of semen sample

EDCs

endocrine-disrupting chemicals - EDCs such as dioxins and polychlorinated biphenyls have been shown to be reproductive toxicants - Others include agricultural pesticides and herbicides, phthalates (used in making plastic materials), lead, and bisphenol A (used in the manufacture of polycarbonate plastic and resins). - solid evidence for lower fecundability and lower birth weight

Asthenospermia

greater proportion of immotile sperm or sperm with decreased motility - attributed to prolonged abstinence, antisperm antibodies, genital tract infections, or varicocele

avoid oil-based lubricant

harmful to sperm

Effects of Obesity and Environmental Factors on Fertility

https://t.me/ProjectTGM/1943

Advantages and Disadvantages of Various Methods for Evaluating Pelvic Anatomy

https://t.me/ProjectTGM/1967 Of the 7 methods; - tubal patency by HSG and laparoscopy only - all except laparoscopy can evaluate uterine cavity - all except HSG can assess developmental defects (but laparoscopy combined with hysteroscopy) - all except HSG and hysteroscopy evaluate ovaries - hysteroscopy, TVS, 3D TVS, and SIS can NOT evaluate for endometriosis and adhesion

Diagnostic algorithm for evaluation of the infertile couple.

https://t.me/ProjectTGM/1969

how to differentiate between dead and nonmotile sperm?

hypoosmotic swelling test - Unlike dead sperm, living sperm can maintain an osmotic gradient. Thus, when mixed with a hypoosmotic solution, living, nonmotile sperm with normal membrane function swell and coil as fluid is absorbed - these viable sperm may be used for intracytoplasmic sperm injection

LPD

lutal phase defect

mittelschmerz

midcycle pelvic pain associated with ovulation

unexplained infertility: prevalence

prevalence reaches up to 30%

Causes of male infertility

roughly be categorized as abnormalities of - sperm production, - sperm function, or - obstruction of the ductal outflow tract Normal sexual function with appropriate deposition of sperm during intercourse is also required.

Asherman sydrome

see cards on "amenorrhea"

Azoospermia

semen present but lacks sperm - 1% of all men - obstructive azoospermia: from outflow tract obstruction as in congenital absence of the vas deferens, severe infection, or vasectomy - nonobstructive azoospermia: follows testicular failure - ways to obtain viable sperm in nonobstructive azoospermia for IVF a. careful centrifugation and analysis may identify a small number of motile sperm b. either epididymal aspiration or testicular biopsy

time it takes for spermatogenesis

spermatogenesis, from stem cell to mature sperm, takes nearly 90 days - Production of sperm requires approximately 70 days. - An additional 12 to 21 days is needed for sperm to be transported into the epididymis where they further mature and develop motility - thus any detrimental event in the prior 3 months can adversely affect semen characteristics - the results of a semen analysis reflect events during the past 3 months, not a single point in time

moliminal symptoms

such as breast tenderness, acne, food cravings, and mood changes

pregnancy rates can rise after HSG Why?

thought to follow flushing of intratubal debris - subsequent spontaneous pregnancy rates may be greater following oil-based dyes rather than water-based ones - Nevertheless, water-based dyes currently remain the preference in most practices as these generally carry a lower allergic reaction risk

infertility: definition

the inability to conceive after 1 year of unprotected intercourse of reasonable frequency