CHAPTER Infertility Basic investigations done in se ofinfertle couple— + Semen Analysis (stinvestigation) + Confirmation of ovulation Baseline scan Assessment of tubal scan Hormonal tests tobe done in lnfertle fernales— +H + FSH + I? hydroxy progesterone + Testosterone + DHEA [LDefinitions > Infertility: failure of a couple of reproductive age to conceive after atleast 1 year of regular coitus without contraception. © Primary infertility: Infertility in a woman who has never been pregnant. > Secondary infertility: Infertility in a woman who has had one or more previous pregnancies » Fecundability: Probability of achieving pregnancy within one menstrual cycle. For a normal couple, this is approximately 25%. > Fecundity: Ability to achieve a live birth within one menstrual cycle Broad Classification of Causes of infertility Wet] [Fees] | [Corned] [Unie eam | | aosomy ioe) ie | Differential Diagnosis of Infer isan oc Nate factors 20 ‘Semen analysis “Tubalterneportoneal "25 HS, laparoscopy, thromepertibalon factors es ‘Anowlabonfovaian actors 25 88T chart, idutoal progesterone level, endometial biopsy, hneiniing hormone testing : Conicalfacors 90 Rost ast ee Unespained infersty 10 Alf he above (Evaluation > Evaluation is indicated! for women who fal to conceive after one or more years of regular, unprotected intercourse. » Women over the age of 35 should be evaluated sooner (ie, after 6 months of regular, unprotected intercourse.) No woman should be denied her request for infertility services or counseling, regardless of duration, > Successful reproduction requires proper structure and function of the entire reproductive axis, including hypothalamus, pituitary gland, ovaries, fallopian tube, uterus, cervix, and vagina > Infertility evaluation comprises eight major elements: © History and physical examination Semen analysis© Sperm—cervical mucus interaction (postcoital testing (PCT))—for select patients 2 Assessment of ovarian reserve 2 Tests for occurrence of ovulation © Evaluation of tubal potency Detection of uterine abnormalities Determination of peritoneal abnormalities > With proper coordination, the evaluation can be completed within one menstrual cycle. No abnormality or cause of infertility can be identified in 10% to 15% of couples. This group comprises a category known as “unexplained infertility.” [LMale Infertility Common Causes [ Endecrine ‘Obaticion of | [Gonadotropin detciney | efferent duct | = Theil astuncon = Congenital Hyperprolactinaeria + Absonce of vas deferens |. Psyenosexuat ‘Young's syndrome ~ Impotence -cgured infection | Erectile dystunction ‘Tuberculosis, gonorhoes Deus ‘Surgical ~Anihypertonsives ‘vasectomy Antipsychotics + Others - Genetic = Elaculatory fare = AT XY (Kineeter) | “ladear neck surgery Y-chromosome deletions ade ejaculation ‘Semen Analysis » The semen analysis is the comerstone of male factor infertility evaluation. Semen sample should be collected after atleast 48 to 72 hr abstinence and is best evaluated within 1 hr of ejaculation. 2 Obtained either by masturbation or by sexual intercourse with a silicone condom, because latex condoms are spermicidal ‘Semen Analysis (WHO-2010) So eo eee Cn Picanto Volume 20 ml ormore (15m) [pence aes f ie eae Viscosity <3 (6caleO-4) Sperm concentration 20 milln/l (15 millon} ‘Total sperm count > 40 milion/ejaculate (39 millon/ ejaculate) = 2 Motity > 50% progressive forward mtlity (Progressive motity=32%) Morphology > 14% nom forn 8) Sees 3 Viability 75¥%ormorelving 8%) lLeucocytes © Less than 1 million/mab. ROS ee ene Round els 25% progressive ragialy progressive Morphology > 15% normal (Stier forms Crtoria) wac < tier immune baad < 1036 frmixed. coated with ‘an globulin antibodies reaction tet When no motle sperms ar| observed a sperm viability test eiferentatesviabie ot fon motile sperms from ead sperms Round celisin semen analysis includes epithelial cells prostate call immature sperms (Gpermatagonia, ound spermatids spermatocytes) and leucocytes. total round celiss> 5 ilion/ imiitisabnormal True leukocytosperrnia means > Villon leukooytes/ml and requires semen culture for mycoplasma homins, ureoplasma vreolyticum and CChlaryeli iymphocytes can be distinguished fom other els by immunoperoxide staining "Ende Test”HERBIE 61 ssosront s Roview: Gyezaoy ‘Men with CAVD suffer with ‘seminal vesicle ageness. So they have low semen volume, ow pH and low fructose levels. Spermatogenesis is normal Other important values in semen Analysis > pH=>7.2 (between 72-78) » Round cells (including WBC + epithelial cells + immature cells) = <5 milion/m. > Sperm agglutination = <2 » The specimen for semen analysis should be collected after 2-3 days of abstinence » The specimen should be obtained by masturbation failing which it can be obtained by coitus interuptus > The specimen should be reach the laboratory within an hour of ejaculation ‘Semen Analysis Terminology > About 5-15% of infertile men suffer from chromosomal abnormalities. Prevalene is higher (10-15%) in men suffering from azoospermia or severe oligospermia. > Always do karyotype analysis in men with azoospermia or severe oligo sper and raised FSH. Klinefelter’s syndrome (XY) is the commonest. Micro deletions of the long arm of Y chromosome can also cause severe seminal abnormalities. Klinefelter’s Syndrome > Karyotype is 47, XXY > Most common genetic anomaly in azoospermic men » Found in 1:500 to 1:1000 live male births. Y-chromosome Microdeletions > May be found in up to 7% of men with male factor infertility > While these men may be able to father children via IVF/ICSI, male offspring will inherit the Y-chromosome microdeletion and be infertile. ‘Congenital Absence of the Vas Deferens (CAVD) » Associated with cystic fibrosis gene mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene > Partners of men with CAVD must be tested for the CFTR gene mutation before pursuing infertility treatment with retrieved sperm. Diagnosis of Male Infertility Inazoospermia the diagnostic test which can distinguish between testicular failure and obstruction of vas deferens is Estimation of FSH levels (see Fig. 9.1) > Avery high FSH would indicate a testicular cause, > Avery low FSH would indicate pretesticular cause,Annormal FSH would indicate a post-testicular cause. retesticular cause-defect ies athe level LH decreased of hypothalamus or play, hence Gnfth FSH decreased decreases , leading to decrease In LH,FSH Testicular volume decreased and Testosterone Testosterone decreased Testicular cause-dotect ies alitie love of | Testosterone docrouse testis hence decreased testosterone , thus So negative feedback on FSH neagtve feecback on FSH is sto FSH Therefore FSHIs increased ineeases Testicular volume is decrease. Post testicular cause FSH normal LHIFSHTestosterone all are normal LH normal Testosterone is normal Testicular volume is normal Fructose Content in the Seminal Fluid coager_ ett Te absence sugges congenital abeence of seminal vesicle or portion of al am Testicular Biopsy te dona to eerie rary tcl Sure fen obtructon a Se Ceara ee ee ee al be sent in Bouin's solution and not in formol saline. Testicular tissues tH FSH) eres emer a vei eee Testis Feedback Transrectal Ultrasound (TRUS) | ipereas ete alee nisms ees ax cennen | aces anges ducts obstruction. Indications of TRUS are: (i) Azoospermia or severe oligospermia with a normal testicular volume, (ii) Abnormal digital rectal examination, (if) Fjaculatory duct abnormality (cysts, dilatation or calcification), (iv) Genital abnormality (hypospadias) Management Options in Male Infertility Mild oligospermia = IUI (Intrauterine insemination) Severe Oligospermia > Hypergonadotropic hypogonadism ({FSH & LH) - Testicular biopsy (to check ‘whether sperms are presentin testis) snotuseful. Donorsperm should beconsidered. > If hormonal levels are normal ~ Testicular biopsy is done. If sperm is present in biopsy, ICSI is the option following retrieval of sperms by TESE and PESA > Men with normal gonadotropin and testosterone level having low volume of gjaculate should be subjected to postejaculatory urine analysis as the patient might be having retrograde ejaculation, In patients of retrograde ejaculation. Sperms are obtained from post ejaculatory neutralised urine and then IUI/ICSI done, Intrauterine insemination is placement of 0.3mL of washed processed and concentrated sperms (devoid of seminal plasma)/ semen into the intrauterine cavity by transcervical catheterization. ia. 94 Fypathelame ptary ‘TESE Testicular sperm SA Pretesticular ididymal sperm aspiration ICSintacytoplasmc sperm Injection All details given ates,Sel Asosment & Revi: Gyozdogy Ucar be done wit patients husbands sperm or donor sperms (in case -of z00- spermia). In case of donors = frozen sperms ate recom mended because of the isk of HIV in fresh sample. The speim donors ate screened for HV, hepautis,sypils, etc and then samples are c1yo preserved, Prerequisite for UI: + Fallopian tube ofthe female should be patent soiecannat be used in tubal inferiligy in females ‘+ Icennotbe used in severe aligospermia (Sperm, count <5 miliony ml) and azoospermia in males ‘The purpose of IUT is to bypass endocervical canal and to place increased ‘number of motile sperms close to fallopian tube. ‘Components of the ejaculate removed in IUI include seminal fluid, excess debris, leukocytes and morphologically abnormal sperms. Best results are achieved when the final specimen contains 10 million total motile sperms, Indi Intrauterine insemination is done in males with: » Severe hypospadiasis > Retrograde ejaculation (Immediate postcoital urine is taken and sperms are extracted from it) » Neurogenic impotence > Sexual dysfunction > Oligospermia > Asthenospermia > Low ejaculate volume In female infertility IULis useful in: > Cervical infertility-Antisperm antibodies are present in cervix > Vaginismus (involuntary contraction of perineal muscles during intercourse) > Unexplained infertil Technique of sperm preparation for IUI (either of the 3) > Swim down technique > Swim up technique |] Shout not be used if sperm count is very lwo > Density gradient centrifugation Procedure Patient is laid in supine position and an insemination catheter is inserted in cervical canal and is advanced slowly in the uterine cavity. 0.5 ml of semen is slowly introduced and patient is then asked to lay supine for 15 minutes. Timing for 1UI > Innatural and clomiphene stimulated cycles, urinary LH monitoring should be started 3 days before expected ovulation and insemination done on the day after midcycle urinary LH surge or IUL is done on 5 and 7 days after completion of clomiphene. > If ovulation is triggered by exogenous hCG, IULis performed 36 hours later. [LICSL intracytoplasmic sperm injectio As the name suggests in this method, the sperm is injected into the cytoplasm of the ova In Males > Oligospermia > Asthenospermia 2 Immune factor (male and female) > Male factor (impotency, hypospadias)couples otiy In Females » Tubal blockage > Hostile cervical mucus > Unexplained infertility Technique (Fig. 9.2) In ICSI the basic steps of oocyte retrieval and embryo transfer are identical to IVF but for fertilisation, one sperm is microscopically injected into one oocyte and the resulting embryo then transferred into the uterus. > Success rate of ICSI following sperm retrieval in obstructive azoospermia is 30- 60%. > Men with obstructive azoospermia need counselling with regard to the transmission of genetic disorder to their offspring, Drawback ICSI is associated with higher congenital anomaly risk (4.2%) when compared with conventional IVE (2-3). ‘As discussed [CSIs the management of choice in males with severe oligospermia and azoospermia. «+ But then friends if male is azoospermic from where do we get the spertns to do (CSI? ‘Answer is simple - azoospermia means sperms are absent in semen but can stil be present the testis. Thus testicular biopsy is done and it sperms are present in testis, thoy aro retrieved by any one ofthe folowing methods. ‘Methods of Sperm Retrieval in Case of Azoospermi (Eh pote (Teoh fnd te inecing (to) pps. a2 > Microsurgical Epididymal Sperm aspiraton : MBSAG soon. 2) The cosa te pert > Percutaneous Epididymal Sperm aspiration : PESAG {6 e ecten Hoan bas mache » Testicular sperm extraction ‘TESE® > Percutaneous Testicular sperm fine needle aspiration : TESA {also called as Fine Neale Aspiration ENA), » The choice of the method depends on: i. the underlying diagnosis, fi, whether goal of the procedure is diagnostic or therapeutic ‘whether, isolated sperm will be used immediately or cryopreserved. TESA + Is ape/culaneous method which requires NovLocal anesthesia and retrieves ‘sperms from the testis when spermatogenesis is normal as in cases of post- testicular azoospermia (.. either there is Congenital absence or obstruction ‘of vas deferensiejaculatory ducts of Retrograde ejaculation), MESA + Also indicated in cases of post testicular azoospermia. itis done when ‘one need's to know the nature of obstruction or If surgical correction of the ‘obstruction is to be performad at the same time ol sperm recovery. (Done "under GA/Regional anesthesia). ‘Another advantage of MESA js that a very age numbar of sperms are Usually relrievad so that cryopreservation and avoidance of repeat surgery ay be possible. Percutaneous epididymal sperm aspiration can also be used in cases of ost testicular azoosperma but it Is @ blind procedure. Bleoding , epididymal injury and postsurgical fibrosis can occur. TESE + Indicated in men with testicular azoospermia or gonadal falure. PESA‘Anowlation isthe most easly treatable cause of female inert In case of anovulation wor an needs to be screened for following underlying patho! ‘ogy leading to anovulation, “Thyroid dysfunction (hypo/typerthyridisn) Hyperprelacineria ‘Weight disorders (excessive weight loss/ best) PCOS Prutary mor ‘Adrenal disease Galactorhes PCOSis the most common disorder encountered inthis category, For details on PCOS see Chapter 13. ‘Common causes of female iforliy =I a hae Exiomalgontatahegina |[uiews fTabes [A Streak gonads (@8x0) | Rigel penneum | Tumours ‘Agenesis |B. Ovulatory dysfunction | Dyspareunia | Adenomyasis |B Block (WHO) (Gupericial and deep) _||+Mulleran anematies|| Clean biock |]. Hypothalamic |. Vaginal septum, agenesis Synechiae (Volowing MT) || ptuitarytarure Cervical atresia - Endometrial ki. Adnesion block |i, Hypathaimiepiitany receptor | Endometriosis ||" dysfunction enovulation sbrocmaly | Nonspecite || (cos) Infection a. Ovarian fire Chiamydia | Postoperative Management of Ovulatory Disorders According to WHO, Ovulatory disorders are grouped into: Group [ Hypothalamic-Pituitary failure: women in this group have hypogonadotrophic hypogonadism, low gonadotrophin and oestrogen level, normal prolactin and negative progesterone challenge test. Included in this group are: stress related amenorthea, Kallmann’s syndrome, anorexia nervosa, Investigations done in these females are > Serum levels of FSH, LH, GnRH, and serum estradiol are estimated. > MRI study is done for the detection of central nervous system pathology. ‘These women are treated with hMG or GnRH. Note: Single most important and effective treatment for this group of women with low BMI (<16 kg/M2) is to encourage gain weight. Leptin is deficient in such women. Exogenous leptin restores ovulation in these women, Group Il: Hypothalamic-Pituitary Dysfunction: Women are normogonadotrophic, norm oestrogenic, anovulatory and oligomenorthoeic. Women with PCOS are in this group. In these women tests for documenting anovulation(discussed below) are clone. These women are treated with clomiphene citrate or other ovulation inducing agents. Group TM: Ovarian failure: Primary ovarian insufficiency (faihure) is the cessation of ovarian function prior to the age of 40 years. It is characterized by primary or secondary amenorshoea with elevated serum gonadotropin levels. Causes of premature ovarian insufficiency (failure) > Abnormal chromosomal pattern (A5XO, 47XXX), causing accelerated follicular atresia > Infections (HIV, Mumps, Tuberculosis) > Iatrogenic: Radiation, Chemotherapy, Surgery (oophorectomy, excessive ovarian drilling) > Metabolic: Galactosemia > Autoimmune disorders (Polyglandular autoimmune syndrome). In most of these females pregnancy can be acheved by using donor ovum, however 5-10% of women achieve pregnancy and deliver successfully by their own ova depending on the ovarian reserve. This indicates, women should be assessed for ovarian reserve before planning management.Tests for Documenting Anovulation Diagrosic of Ovation ee ee! inact Direet Concave T T Taparosiony Bramnaney ‘Basal Body Temperate apical Muale Sua) Vaginal Cveogy Inavultony cycle, there ss Underine inf uance of sesirogen| | Maturtion index sits Diohasie® pater ofrmperature| |oervieel mucus shows fering | | 10 left under the eflect ‘variation, At the time oF lor stetchabity (spinberkei) of progesterone alter covulation BBT 8 raised "Alter ovulation progesterone | | ovulation DS ter. Therese custains | {causes los of erning and throughout the 2nd haifotthe | |stetchabliy™ Persistence of ‘yc and falls two days prior | |feming/spinbarkelt beyond 22nd {erent period -caled biphasic | |days means anovuation ® patton n pregnancy - Rise 2 Of temperature is sustained. In ‘ovulatory eyee “No Rise of ‘emporature through - out the eyes TT [Hormonal Esimaton Endorial Boos) use |S progesterone: done on_| |itshoula be cane an 21-23" | | Serial sonography can ‘hand 2tst'day ofeycle. | | day of rogular cyt. | [precisely measure te size An inereese in val rom <1 | |invease oflreguiercyciestt | | of Grafflan folile, and thus mgimito->6 maim suggests | |1sdone wkhin24 hours oftie | | the exact tine of ovuaten, ‘ovulation period Features®olecent | Serum LH or Urine LH Enaing wlaton® are colapsed LR ostimation dally can Evidence of secretary activity (lt || folele and fuid in pouch of indicate LH eurge end LM | |the acton of progesterone) =| | Doughas, Deak, Ovulation occurs 10-12) | elagnostcof ovulation fr ater LH peak ™ | Serum oestradiol It tains Deak 24 hours prior to LH surge Management of Anovulation is by ovulation induction, Ovulation induction aims at the release of one egg per cycle in a woman who has not been ovulating regularly. Ovulation Inducing Agents > Clomiphene citrate (CC) > Letrozole > Gonadotropins ‘Clomiphene Citrate: It is a racemic mixture of enclomiphene and zuclomiphene. Enclomiphene is a more potent isomer responsible for its ovulation-inducing action. > Dose = 50-250 mg. However, the US FDA-approved maximum dose for clomiphene citrate is 100 mg > Clomiphene blocks “Estrogen” receptors —+ increase FSH from pituitary — growth of follicles > Thusit can be used only in patients with intact hypothalamic -pituitary ovarian ax > With clomiphene success rate for ovulation is 80% and success rate for pregnancy is 40% Letrozole: It is an aromatase inhibitor which blocks the conversion of testosterone to estrogen, leading to increased FSH from pituitary. Gonadotropins: HMG (Human Menopausal Gonadotropin obtained from the urine of the menopausal women) and recombinant FSH. chester 9 veraty REE IMC used drug for ovulation induction: clomiphene crate + Letraole is now not availabe in the market due tothe associated risk ofteratogenecty. ‘Clomiphene — Risk of multiple pregnancy = 5-10% eG i$ functionally and structural simlartoLH hence Giving LH injection creates LH surge like condition,Sal Assos & Revi: Gynecology » Menopausal women have high FSH and LH levels in their blood and urine, and HMG is extracted from urine of menopausal females, Note: » Recombinant LH is can also be used but is very expensive » Follicular study is done along with ovulation induction to monitor the growth of follicles and when the dominant follicle is 18-20 mm, ovulation trigger is given to rupture the follicle » Forovulation trigger, M/C drug used is hOG (derived from the urine of pregnant ‘women or by recombinant technology) > Ovulation cccurs 36 hours after injecting hCG Side Effects of Ovulation Induction > Multiple pregnancies: 5-10% with clomiphene, 15-30% with Gonadotropins > Ovarian hyperstimulation syndrome (OHSS) > Most dangerous complication of ovulation induction © Risk factors: Young age, low body weight, PCOS patients and past history of OHSS [LOvarian Reserve Ovarian reserve tests are to assess the quantity as well as the quality of primordial follicles present in the women’s ovary. These tests are done to determine how the ovaries will respond to therapy (ovulation induction) in other words it is the assessment of the reproductive potential of the woman, The Tests Done Are Estimation of basal level of serum FSH on D3 and again on D10 following clomiphene citrate challenge test (CCT): 100 mg orally each day from D5-D9: resene'sSeumDay3FSH | values >10 IU/L (more than 25D) indicates poor ovarian reserve. tevels > Basal (D3) serum estradiol level > 70-80 pg/mL, poor ovatian reserve, > Serum inhibin B (D5): Reduced inhibin B levels (less than 40 pg/mL) are observed in woman with advanced age. > Serum antimiillerian Hormone (AMH): Levels of serum AMH is a good predictor of ovarian stimulation response. Its level also comes with the direct proportion of antral follicle count. Levels of AMH (Ing/mL) declines with age and with poor ovarian reserve. Levels of AMH can be measured any time in the menstrual cycle. AMH: AMH is produced by the granulosa cells of the preantral small follicles, Serum levels of estradiol and inhibin B depend on pituitary FSH feedback mechanism. Level of AMH is not dependent on feedback mechanism. This is one of the reasons for which AMH is being consicered as a better predictor of ovarian reserve compared to estradiol and inhibin B. Levels of AMH can be measured at anytime in the menstrual cycle. It therefore understood that AMH is qualitative whereas Antral Follicle Count (AFC) isa quantitative marker of ovarian reserve. ‘Antal Follicle Count (AFC) is done by using TVS in early follicular phase in both the ovaries. ARC reflects the primordial follicular pool in the ovary. > AFC more than 6 2-10 mm size) refleets adequate ovarian follicular reserve. > ABC, less than 4, indicates poor ovarian reserve and poor response to ovarian stimulation during IVF. » AFC decreases with age. Best indicator of ovarian[Ltubal Factors ‘Tubal factors leading to infertility include endometriosis, pelvic adhesion disease or previous bilateral tubal ligation. Tests for Detecting Tubal Potency Ist test/Initial test-Hysterosalpingography (HSG) > Hysterosalpingogram (HSG) assesses uterine and fallopian tube contour and tubal patency. Itshows Mallerian anomalies as well as most endometrial polyps, synechiae and submucosal fibroids, It can also determine tubal patency. © Performed in the early follicular phase, within 1 week of cessation of menstrual flow, to minimize chances of interrupting a pregnancy. 9 The procedure is performed by injecting a radiopaque dye through the cervix. ‘As more dye is injected, the dye normally passes through the uterine cavity into the fallopian tubes and then spills into the peritoneal cavity. X-ray films are taken under fluoroscopy to evaluate tubal patency. © Nonsteroidal anti-inflammatory drugs may be given to prevent cramping. ° HISG may have therapeutic effects. Several studies have indicated increased. pregnancy rates for several months after the procedure. 2 Prophylactic antibiotics (doxyeycline, 100 mg orally twice daily for 5 to 7 days) are advisable when the patient has a history of pelvic inflammatory disease or when hydrosalpinges are identified during the study. > Saline infusion ultrasonography (Sonohysterography (SHG)) © SHG involves transvaginal ultrasound after the introduction of sterile water or saline into the uterine cavity. Useful in assessment of uterine cavity abnormalities such as polyps ot submucosal fibroids. > Diagnostic laparoscopy/Chromopertubation © This is the most definative and most invasive step in the patient's evaluation. © Assesses peritoneal and tubal factors, such as endometriosis and pelvic adhesions and can provide access for simultaneous corrective surgery. ‘© Laparoscopy should be scheduled in the follicular phase, 9 Chromopertubation: Dye (usually a dilute solution of indigo carmine) is instilled through the fallopian tubes during laparoscopy to visually document ‘tubal patency, Management of Tubal Factor Infertility > Proximal tubal obstruction is identified on HSG. Tubal spasm may mimic proximal obstruction, however, and obstruction should be confirmed by Iaparoscopy. Treatment consists of tubal cannulation, microsurgical tubocornual reanastomosis, or IVF. > Distal tubal disease or distortion can be seen on HSG and laparoscopy. The success of corrective surgery (neosalpingostomy) depends on the extent of disease. Best is IVF. > For patients with a history of a prior bilateral tubal ligation who desire fertility, options include microsurgical sterilization reversal as well as IVF. ‘© Success of tubal reanastomosis depends on age, type, and location of the sterilization procedure and final lengths of repaired fallopian tubes. 2 IVE may be a better option for these patients who desire only a single additional child, chptoo_wority ES First test to assess tubal potency HSG. + HSGisnotthe best test because iteannot ferentiate between ‘comual spasm and cormual blockade. * Obsolete test fortubal patency —Rubinstes/O, inuflation test ‘+ Bestest ~ Laparoscopic chromopertubatlon, Laparoscopy with chromper- tubation Is the best invest- gation for confirming, tubal patency and, besides, any pa- thology can. simultaneously bbe cartecied with operative laparoscopy, As it requires general anaes- thesia andl admission, so tis ot the fst line investigation ‘or tubal patency. Best management of Tubal Factory inferttys VF Intra uterine insemination isnt useful in case of tubal factory infertityset Asoseont & even Geode) Mnemonic for uses of MF in females: T= Tubalinferity R= Recanalsation after tubal sterilisation © = Ovarisn flue or diminshed ovarian reserve using donor oocytes) = Females with Cancers ot on Chemotherapeutic drugs ‘A= A1DSin partner R= Fiskofransmiting genetic disease to offering = Surtogate motherhood if patienthas no functional uterus. Fertilisation is documented by the presence of wo pronucll and extrusion of second polar at 24 hr [Lin vitro Fertilization (IVF) IVEwasfirst developed as a means to overcome infertility resulting from irreparable tubal disease as fertilization takes place in fallopian tube, Now the spectrum of IVF has broadened and is indicated in number of conditions - In Femal Infertility » Tubal pathology resulting from previous infection or advanced stages of endometriosis or in cases with proximal and distal obstruction. > In women desiring reversal of tubal sterilization with poor prognosis for recanalization? > Ovarian failure and Diminished ovarian reserve: Here IVF is performed using donor oocytes.2 > Women recently diagnosed with a cancer or another medical disorder facing eminent treatment (chemotherapy and radiotherapy) that poses a serious threat to their future fertility. Such women can have cryopreservation of their embryos and later IVF done. > Women with normal ovaries but no functional uterus as a result of a congenital anomaly (mullerian agenesis),ES exposure, advanced disease (multiple myeloma, severe intrauterine adhesions) or a previous hysterectomy can be afforded the opportunity to have their own genetic offspring via IVE with transfer of embryos to the uterus of a surrogate.® > Women who carry genetic risk or disorder which may be expressed in their offspring can be the candidates for IVF with preimplantation genetics to identify and exclude affected embryos.2 > HIV positive serodiscordant couples -use of ICSI or sperm washing techniques has enabled HIV negative women to safely achieve pregnancy using the sperm of their affected male partners. In Male Infertility > When sperm court is <5 million/ ml > Repeated [UI failure > Multifactor infertility? > Unexplained infertility’ Since, we have to choose one option: Tubal pathology ie. option ‘a’ is the best option? Basic Steps of IVF > Sperms are retrieved from male partner. > Ovarian stimulation is done with gonadotropins and follicular monitoring is done > When ova reaches 20mm in size injection hCG is given to trigger ovulation. > Oocytes are then retrieved (ovum pickup) through a 17 gauge needle passed through the vaginal fornix » For fertilization: 50,000 to 100,000 sperms are put on each oocyte retrieved, in a petridish » Embryos are kept in incubator for 48-72h > After fertilisation embryo transfer is done on day 2 or day 3 (48-72h) after oocyte insemination Note Day 5 blastocyst transfer is becoming more common today due to higher live births compared to cleavage stage(day 3) embroyos. > Generally 3-4 embryos are transferred in the uterine cavity (thus chances ofmultiple pregnancy are high with IVF), and deposited 1 cm below the fundus (the usual site of implantation), > Success rate of IVF per cycle is 30-35% > Excess embroyos not used for transfer can be cryopreserved for an unlimited period, with a survival rate of 75%: Cervical Factory Infertility Cervical factor inferti Cervical factor infertility i Infection | ji. Prior cervical surgery ii, Use of antiesiragens (2.9. clomiphene citrate) for ovulation induction rescence of Anisperm antibodies The treatment of cervical factor depends on the cause > Ifit is due to chronic cervicultis/infection - Treatment of infection by antibiotics is the cure > Ifis due to decreased mucus volume - Treatment includes short-term supple ‘mentation with exogenous estrogen like ethinyl estradiol and use of mucolytic cexpectorant like guaifenesin. However, their value has not been confirmed > Ifitis due to antisperm antibodies -Investigation done to detect antibodies, deficient mucus due to Post Coital Test (Sims or Huhner’s Test) tis designed to assess: > The quality of cervical mucus. > Presence and number of motile sperms in the female reproductive tract after coitus. > Interaction between cervical mucus and sperms. > It gives an approximate idea of sperm count: (rormeally 10 ~ 50 motile sperms are seen per high potoer field in cervical mucus, if count is <10 sperms / HPF it indicates the need far complete semen analysis). ‘Time of test: > Itshould be performed 1 or 2 days before the anticipated time of ovulation, when ‘maximum estrogen secretion is present. > For patients with irregular cycles, patients urinary LH surge may be helps scheduling the test. Method: The couple is advised to have intercourse and present to the doctor within 2-12 hours of intercourse.The cervial mucus of the female partner is collected and examined under microscope, ein Number of motile sperms/ HPF Preowuiatory conical mucus” Atleast 13 30 mote (under th ituence of spormsiHPF shouldbe estrogen) is clear, watery, ‘seen. i Abundant and srechabie i (epinbarket > 8-10 om) with i 00 tela fering and iow’ i | | ' Quality of cervical mucus: Motility of sperms: T+ Nonnally sperms show progressive movement ‘and not rotatory ‘of movement. The fpresencs of anti sperm antibodies in the cervical) mucus imparts otatary ‘on shaking movement tothe sperm orrenders | them completely immoiite. cellularity ‘Characteristic of Progesterone stimulated mucus: = Thick & opaque ~ Lacks ferning i = Breaks (take) on stretching pry Prerequises for the test ~ Abstinence of2 days! Intercourse to be performed 2- 12 hours before the test? = Nose of lubricant? Post cota est isonlya 3g test for detecting antisperm antibodies, Confirmatory tests for detecting antisperm + Sperm agglutination test + MAR (mbeed soglut rection) Test. + Immunabead test Tests for studying sperm function Sperm Penetration efor assay? suthng perm Milles kurrok test? penetration Hypoosmotic swelling tet: Test for studying tal function, Hemizona Test Test or studying the abity of sperm tobind to hurnan zona pellucida,HEREBY s Asccononea evn Gyneeseny fibroid leading to abortions and infertility is submucous flroi > Treatment options include: Use of condom or diaphragm as a barrier method for 3 months, During this period, ‘the antibodies will disappear and conception may occur then, 2 Corticosteroids given to female partner can also help in getting rid of these antibodies. © Intrauterine insemination at the time of ovulation (most acceptable method for cervical factor infertility) or GIFT (Gamete intrafallopian transfer) are very useful techniques in such cases. IUL is the best method for treating cervical factor infertility and unexplained infertility. So many clinicians forgo cervical mucus testing and proceed directly to TUL treatment in absence of tubal disease. Uterine Factors Uterine factors, suchas submucous leiomyomas, intrauterine synechiae (Asherman’s syndrome), and uterine cleformities or septa, cause approximately 2% of infertility. ‘The mainstay of treatment for these conditions is surgical correction, frequently hysteroscopic approach. Luteal Phase Defect During normal luteal phase when their is adequate progesterone secretion by the corpus luteum, adequate development of secretory endometrium occurs for blastocyst implantation. Luteal phase defect refers to a condition when production of progesterone is suboptimal by corpus luteum. Itis an inevitable phenomenon in all ART cycles, LPD may cause implantation faikure and is thought to account for 4% of infertility. Diagnosis of LPD is not based on uniform criteria > Low levels of midluteal serum progesterone (<10 ng/mL) > Endometrial histology done on 25th -27 th day of cycle shows endometrium >2 day out of phase > A shortened luteal phase <14 days, are considered for the diagnosis. ‘Management - Micronized Progesterone [LPreimplantation Genetic Diagnosis (PGD) PGD allows couples with various single-gene disorders and X-linked genetic diseases to avoid transmission of the disorder of offspring, » Proceeds by biopsy and genetic analysis of one of the following specimens: © 1to2 blastomeres of a cleavage-stage (days 2 to 3) embryo derived from IVF. Polar body biopsy from a metaphase Il oocyte obtained after COH. 2 Trophectoderm tissue from a blastocyst-stage (day 5) embryo. > Single-Gene Disorders © Using the polymerase chain reaction (PCR), DNA extracted from the biopsy specimen is used to screen for a known hereditary disorder—for example, cystic fibrosis, muscular dystrophy, and Huntington's disease. © Only unaffected preimplantation embryos would be transferred to the ‘woman's uterus.