Anovulation- the most Anovulation- the most frequent cause of female frequent cause of female

infertility. infertility. It can be connected with:It can be connected with:

Irregular menstruationIrregular menstruation OligomenorrheaOligomenorrhea AmenorrheaAmenorrhea Regular menstruations can also Regular menstruations can also

occuroccur

Anovulation- the reasons:Anovulation- the reasons:

HyperprolactinemiaHyperprolactinemia Hypothalamic- pituitary dysfunctionHypothalamic- pituitary dysfunction Ovarian failureOvarian failure PCOPCO

Diagnostic methods:Diagnostic methods: PRL/MCP, FSH, LH, EPRL/MCP, FSH, LH, E22 serum serum

concentrations between 3 - 6 day of cycle.concentrations between 3 - 6 day of cycle. P test and ultrasound ovarian assessment.P test and ultrasound ovarian assessment.

Hyperprolactinemia:Hyperprolactinemia:

PRL > 20 ng/ml, MCP > 300%PRL > 20 ng/ml, MCP > 300% Causes: stress, hypothalamic failure, PCO, Causes: stress, hypothalamic failure, PCO,

psychotropic drugs (e.g. trnquilizers), rare - psychotropic drugs (e.g. trnquilizers), rare - adenomaadenoma

When PRL>27.8 ng/ml determine TRH - When PRL>27.8 ng/ml determine TRH - hypothyreosis?hypothyreosis?

Syndroms: Oligomenorrhea or amenorrhea, Syndroms: Oligomenorrhea or amenorrhea, infertility- anovulation, deficient activity of the infertility- anovulation, deficient activity of the corpus luteum, galactorrhea in 33%.corpus luteum, galactorrhea in 33%.

Treatment: BromocriptineTreatment: Bromocriptine

Hypothalamic- Pituitary Hypothalamic- Pituitary dysfunctiondysfunction

P test - negative, FSH, LH <5 mj/ml or normal, P test - negative, FSH, LH <5 mj/ml or normal, E2<40 pg/mlE2<40 pg/ml

Causes: the most frequent congenital Causes: the most frequent congenital hypothalamic- pituitary insufficiency, stress, hypothalamic- pituitary insufficiency, stress, excessive exercise, weight loss, malnutrition.excessive exercise, weight loss, malnutrition.

Management:Management:– EliminationElimination risk factors risk factors– GnRH GnRH – hMH, FSHhMH, FSH

Ovarian failureOvarian failure

FSH >20mj/mlFSH >20mj/ml Possible in each age:Possible in each age: In younger women (age 30) frequently In younger women (age 30) frequently

genetic causes- karyotype evaluation.genetic causes- karyotype evaluation. In woman atIn woman at reproductive age it can be reproductive age it can be

transient or permanent.transient or permanent. Causes:Causes: idiopathic, autoimmunological- idiopathic, autoimmunological-

thyroid inflammation, myasthenia, thyroid inflammation, myasthenia, thrombocytopenia, rheuamtoid disease, thrombocytopenia, rheuamtoid disease, adrenal failure, vitiligo, hemolytic anemia. adrenal failure, vitiligo, hemolytic anemia. past surgeries, chemio- or radiotherapy, past surgeries, chemio- or radiotherapy, inflammations, 17- hydroxylase hypoactivity, inflammations, 17- hydroxylase hypoactivity, hormonal ovarian resistance.hormonal ovarian resistance.

Ovarian failure- Ovarian failure- treatmenttreatment

E/P, in women at the beginning of E/P, in women at the beginning of

ovarian failure ovulation can be ovarian failure ovulation can be

restored in about 20% of women.restored in about 20% of women. hMG treatment is ineffectiveness and hMG treatment is ineffectiveness and

autoimmunologic process can intensifyautoimmunologic process can intensify

Variety of syndroms in Variety of syndroms in PCOPCO according to Balen et al.according to Balen et al.

Obesity 38 - 50%Obesity 38 - 50% DysmenorrheaDysmenorrhea Infertility in 75% Infertility in 75% Hyperandrogenism in Hyperandrogenism in

48%48% Without syndroms 20%Without syndroms 20%

Hormonal diagnostics:Hormonal diagnostics: T, AT, A LHLH LH:FSHLH:FSH Insulin level in fasting Insulin level in fasting

statestate PRLPRL SHBGSHBG

Body weight Body weight reductionreduction

Decreasing the E1 and LH Decreasing the E1 and LH

concentrationsconcentrations

Decreasing the P 450C activity and Decreasing the P 450C activity and

free Testosterone concentrationfree Testosterone concentration

MetforminMetformin

Decrease the insulin level and Decrease the insulin level and

restore correct steroidogenesisrestore correct steroidogenesis(take place the proper cytochrome P 450 C 17 (take place the proper cytochrome P 450 C 17

alfa phosphorylation)alfa phosphorylation)

INFERTILITY INFERTILITY DIAGNOSISDIAGNOSIS

Hysterosalpingography Hysterosalpingography (HSG)(HSG)

Hysterosalpingogram- x-ray imaging Hysterosalpingogram- x-ray imaging of the uterus and fallopian tubes of the uterus and fallopian tubes after instillation of a contrast liquidafter instillation of a contrast liquid

Routine infertility evaluation (basic Routine infertility evaluation (basic test)test)

Assess morphology of endocervical Assess morphology of endocervical canal, uterine cavity, tubes. canal, uterine cavity, tubes.

Rule out tubal occlusion, synechiae, Rule out tubal occlusion, synechiae, uterine anomalies. uterine anomalies.

Contraindications to Contraindications to HSG:HSG:

1.1. active PID with abdominal active PID with abdominal tenderness or palpable mass tenderness or palpable mass

2.2. recent uterine/tubal surgery recent uterine/tubal surgery

3.3. active uterine bleeding active uterine bleeding

4.4. pregnancy (schedule exam pregnancy (schedule exam before ovulation to avoid before ovulation to avoid early pregnancy) early pregnancy)

Normal hysterosalpingogram.Normal hysterosalpingogram.A smooth triangular uterine cavity and A smooth triangular uterine cavity and

spill from the ends of both tubes.spill from the ends of both tubes.

HSG showing a normal uterus and HSG showing a normal uterus and blocked tubesblocked tubes

No "spill" of dye is seen at the ends of the No "spill" of dye is seen at the ends of the tubestubes

Hysterosalpingogram showing a uterus Hysterosalpingogram showing a uterus with a myoma that is pushing in to the with a myoma that is pushing in to the

cavity.cavity.

A hysterosalpingogram indicate A hysterosalpingogram indicate intrauterineintrauterine adhesionsadhesions ( (synechiasynechia))

Tubal Recannulization and Tubal Recannulization and Selective SalpingographySelective Salpingography

                                                                    

                                                                  

Selective hysterosapingography, or Selective hysterosapingography, or proximal tubal cannulization may open proximal tubal cannulization may open

the tubes avoiding surgery.the tubes avoiding surgery.

LAPAROSCOPY

The camera and instruments are inserted into The camera and instruments are inserted into the abdomen or chest through small skin cuts the abdomen or chest through small skin cuts

allowing the surgeon to explore the whole cavity allowing the surgeon to explore the whole cavity without the need of making large standard without the need of making large standard

openings dividing skin and muscle.openings dividing skin and muscle.

After the cut is made in the umbilical area a After the cut is made in the umbilical area a special ( Veress) needle is inserted to start special ( Veress) needle is inserted to start

insufflation. A pressure regulator CO2 insufflator insufflation. A pressure regulator CO2 insufflator is connected to the needle. The pressure is connected to the needle. The pressure obtained should not be beyond 15 mmHg.obtained should not be beyond 15 mmHg.

After satisfactory insuflation the After satisfactory insuflation the needle is removed and a 10 mm needle is removed and a 10 mm trocar is inserted through the trocar is inserted through the

previous umbilical wound.previous umbilical wound.

Laparoscopic view of a normal pelvis.Laparoscopic view of a normal pelvis.Uterus in midline. Tubes and ovaries Uterus in midline. Tubes and ovaries

(white structures) also visible.(white structures) also visible.

Contraindications to Contraindications to laparoscopy:laparoscopy:

Circulatory and respiratory Circulatory and respiratory insufficiencyinsufficiency

Hypovolemic shockHypovolemic shock IleusIleus PeritonitisPeritonitis Abdominal or diaphragmic Abdominal or diaphragmic

herniahernia Tumors in abdominal cavityTumors in abdominal cavity

Pelvic laparoscopy is Pelvic laparoscopy is also not recommended also not recommended

for patients with:for patients with:

– severe obesity severe obesity – existing severe pelvic existing severe pelvic adhesions from adhesions from previous previous surgeriessurgeries

Pelvic Laparoscopy: Pelvic Laparoscopy: RisksRisks

Risks for any anesthesia are: Risks for any anesthesia are: • reactions to medications reactions to medications • problems breathing problems breathing

Risks for any surgery are: Risks for any surgery are: • bleeding bleeding • infection infection • damage to adjacent organs damage to adjacent organs

HYSTEROSCOPYHYSTEROSCOPY Assess the endocervical canal, Assess the endocervical canal,

uterine cavity and uterine uterine cavity and uterine openings of the oviducts.openings of the oviducts.

Enables to make the intrauterine Enables to make the intrauterine operations.operations.

Hysteroscopic view of a uterine septum.Hysteroscopic view of a uterine septum.A septum can cause recurrent A septum can cause recurrent

miscarriage. miscarriage.

A large polyp at the top of the uterine cavity

Contraindications to Contraindications to hysteroscopy:hysteroscopy:

Infections of reproductive Infections of reproductive organsorgans

Massive bleeding from uterusMassive bleeding from uterus PregnacyPregnacy Cervical cancerCervical cancer

Hysteroscopy. Hysteroscopy. Risks.Risks.

Uterine perforationUterine perforation BleedingBleeding InfectionInfection Pulmonary embolism (rare)Pulmonary embolism (rare)

Polycystic ovarian syndrome (PCOS) occur Polycystic ovarian syndrome (PCOS) occur inin 5-10% of reproductive-aged women5-10% of reproductive-aged women

PCOS PCOS ovulatory dysfunction or absent ovulatory dysfunction or absent ovulation ovulation infertility infertility

infrequent or irregular infrequent or irregular menstrual menstrual cyclescycles

absence of ovulation absence of ovulation no progesterone no progesterone production in the second half of the production in the second half of the menstrual cycle menstrual cycle the risk for an the risk for an abnormal buildup of the lining of the abnormal buildup of the lining of the uterus (endometrial hyperplasia) or uterus (endometrial hyperplasia) or cancer.cancer.

Another feature to PCOS is clinical or Another feature to PCOS is clinical or laboratory hyperandrogenism laboratory hyperandrogenism increased circulating amounts of or increased circulating amounts of or increased responsiveness to "male" increased responsiveness to "male" hormones like testosterone or DHEAShormones like testosterone or DHEAS

Symptoms: oily skin or acne and Symptoms: oily skin or acne and excess hair on the face, between the excess hair on the face, between the breasts, or on the lower abdomen.breasts, or on the lower abdomen.

Changes in the ovaries in Changes in the ovaries in ultrasoundultrasound

Ultrasound findings: poly (many), Ultrasound findings: poly (many), cystic (small collections of fluid). cystic (small collections of fluid).

The eggs in the ovaries do not The eggs in the ovaries do not develop to maturity develop to maturity many small many small "follicles" (small fluid-filled sacs "follicles" (small fluid-filled sacs containing immature eggs) seen on containing immature eggs) seen on ultrasound. ultrasound.

The ovaries of women PCOS are The ovaries of women PCOS are often enlarged as well.often enlarged as well.

Another common feature of PCOS is Another common feature of PCOS is increased body weight and trouble increased body weight and trouble in losing weight.in losing weight.

Mechanism: insulin resistance (the Mechanism: insulin resistance (the cells of women with PCOS do not cells of women with PCOS do not respond as well to their bodies' own respond as well to their bodies' own insulin) insulin) women with PCOS are at women with PCOS are at higher risk for developing diabetes higher risk for developing diabetes during pregnancy or later in life.during pregnancy or later in life.

Treatment StrategiesTreatment Strategies

The aim: to help regulate menstrual cyclicity and The aim: to help regulate menstrual cyclicity and prevent endometrial hyperplasia. prevent endometrial hyperplasia. Oral contraceptives (birth control pills- Oral contraceptives (birth control pills- BCPs)BCPs). BCPs also help reduce acne and facial . BCPs also help reduce acne and facial hair in most patients with PCOS.hair in most patients with PCOS.In women who do not require oral contraception, In women who do not require oral contraception, progesteroneprogesterone given for 10-12 days every 30- given for 10-12 days every 30- 60 days will induce a reliable menses.60 days will induce a reliable menses.For women with PCOS who desire pregnancy, For women with PCOS who desire pregnancy, ovulation inductionovulation induction (COH)(COH) is often necessary. is often necessary.Drugs that increase insulin sensitivity in PCOS- Drugs that increase insulin sensitivity in PCOS- Metformin Metformin help induce ovulation help induce ovulation

help women to lose weighthelp women to lose weight

In women who cannot tolerate oral In women who cannot tolerate oral medications or have failed several medications or have failed several different regimens of medication, different regimens of medication, surgical induction of ovulation can surgical induction of ovulation can also be attempted (laser or also be attempted (laser or electrosurgical techniques to place electrosurgical techniques to place small holes in the ovaries in an small holes in the ovaries in an effort to normalize the hormonal effort to normalize the hormonal environment and allow ovulation environment and allow ovulation to occur)to occur)

ANDROLOGYANDROLOGY

Dr hab. Rafał KurzawaCLINIC of REPRODUCTION and

GYNECOLOGY

POMERANIAN ACADEMY of MEDICINE

Infertility- Infertility- epidemiologyepidemiology

Symptomatology of male Symptomatology of male infertility infertility

TYPE I TYPE I – erection problems – erection problems (0,3-7%)(0,3-7%) TYPE II TYPE II – azoospermia – azoospermia (0,9%-16%)(0,9%-16%) TYPE III – immunological infertility TYPE III – immunological infertility (3,4%-25%)(3,4%-25%) TYPE IV – abnormal seminal quality TYPE IV – abnormal seminal quality (23%-(23%-

48%)48%) TYPE V TYPE V – idiopathic sperm dysfunction – idiopathic sperm dysfunction (0-(0-

25%)25%)

DiagnosisDiagnosis General examination General examination Semen analysis Semen analysis Other diagnostic tests: Other diagnostic tests:

– USGUSG– Hormonal diagnostic Hormonal diagnostic – Diagnostic tests for Assisted Reproductive Diagnostic tests for Assisted Reproductive

Technology Technology

TYPE I – erection problems TYPE I – erection problems (0,3-7%)(0,3-7%)

Normal ejaculation Normal ejaculation – Hypospermia (semen volume < 2,0 ml) – chronic Hypospermia (semen volume < 2,0 ml) – chronic

prostatitis prostatitis – Impotence Impotence

Retrograde ejaculation Retrograde ejaculation – Neurogenic– DM, SM Neurogenic– DM, SM – Anatomical Anatomical – Jatrogenic – drugs, operations Jatrogenic – drugs, operations

disejaculation disejaculation – Functional – anorgazmiaFunctional – anorgazmia– Neurogenic – spinal injury Neurogenic – spinal injury – Jatrogenic – drugs, chemiotherapy, radiotherapy, Jatrogenic – drugs, chemiotherapy, radiotherapy,

operations operations

TYPE II – azoospermia TYPE II – azoospermia (0,9%-16%)(0,9%-16%)

Pre-testicular causes Pre-testicular causes – Hypothalamic or pituitary disorder – LH, FSH Hypothalamic or pituitary disorder – LH, FSH

deficiency, Kallman syndrome, trauma, tumors, deficiency, Kallman syndrome, trauma, tumors, inflammation, meningitisinflammation, meningitis

Testicular causes Testicular causes – Primary testicular failure Primary testicular failure – Congenital – 47XXY, del Y, AZFCongenital – 47XXY, del Y, AZF– Acquired- mumps, testicular torsion, castrationAcquired- mumps, testicular torsion, castration– Jatrogenic – radiotherapy, chemiotherapy Jatrogenic – radiotherapy, chemiotherapy

Post-testicular causes Post-testicular causes – Congenital – CBAVD, CFCongenital – CBAVD, CF– Acquired – inflammations (gonorrhea) Acquired – inflammations (gonorrhea) – Jatrogenic – vasectomy, hernia operationJatrogenic – vasectomy, hernia operation

Diagnostic tests for Diagnostic tests for Assisted Reproductive Assisted Reproductive TechnologyTechnology- ICSI- ICSI

FSHFSH– If < 12IU – sperm biopsy If < 12IU – sperm biopsy

is effective in 80-90% is effective in 80-90% Blocked ejaculatory Blocked ejaculatory

duct duct (Micro-Epidydymal (Micro-Epidydymal Sperm Aspiration –Sperm Aspiration –MESE) MESE)

Other Other (Testicular Sperm (Testicular Sperm Extirpation- TESE, Extirpation- TESE, Testicular Sperm Testicular Sperm Aspiration- TESA) Aspiration- TESA)

TYPE III – immunological TYPE III – immunological infertility infertility (3,4%-25%)(3,4%-25%)

antisperm antibodies antisperm antibodies – the immune system – the immune system may produce may produce antibodies that antibodies that attack and weaken or attack and weaken or disable spermdisable sperm – Auto-Auto-

immunological immunological diseases diseases

– Concequences of Concequences of testicular traumatesticular trauma

Congenital Congenital – Undescended testicles Undescended testicles

Sexually transmitted Sexually transmitted

disease (gonorrhoea) or disease (gonorrhoea) or testicular infection testicular infection (mumps) (mumps)

Vascular Vascular – Testicular torsion Testicular torsion – Varicocoeles Varicocoeles

Diseases: Diseases: – Thyroid faiure; Thyroid faiure;

Addison disease, Addison disease, hepar diseases; DM, hepar diseases; DM, auto-immunological auto-immunological diseases; diseases;

Environmental factorsEnvironmental factors– Drugs (sulfasalazine, T, Drugs (sulfasalazine, T,

chemiotherapy)chemiotherapy)– Temperature Temperature – Other factors (X-rays, Other factors (X-rays,

lead, cigarette smoke, lead, cigarette smoke, alcohol; marijuana, alcohol; marijuana, frequently wearing frequently wearing tight-fitting pants and tight-fitting pants and underwear)underwear)

Immunological Immunological – Testitis Testitis

Genetic Genetic – del Y, aberrations (count del Y, aberrations (count

and structure of and structure of chromosomes) chromosomes)

Idiopathic [46%] Idiopathic [46%]

TYPE IV – abnormal sperm TYPE IV – abnormal sperm quality quality (23%-48%)(23%-48%)

Morphologic imagesMorphologic images

TreatmentTreatment

Risk factor elimination Risk factor elimination Give up smoking Give up smoking Testicular temperatue decreaseTesticular temperatue decrease Regular sexual intercourses (2-3 per Regular sexual intercourses (2-3 per

week) week) Antioxydants Antioxydants

– Vitamin E, C, Zinc Vitamin E, C, Zinc Tetracicline Tetracicline

– Chlamydia Trachomatis infection Chlamydia Trachomatis infection

Treatment Treatment (pharmacotherapy)(pharmacotherapy)

Risk factor elimination Risk factor elimination Hormonal treatment Hormonal treatment

– Testosterone Testosterone – hCGhCG – FSH FSH – C.C, tamoxyphen C.C, tamoxyphen

Varicose veins in the Varicose veins in the spermatic cordspermatic cord

Physical examination Physical examination – I I Valsalva test examination ( or during Valsalva test examination ( or during

cough) cough) – II II large veins during palpation large veins during palpation – IIIIII visible varicouse veins visible varicouse veins

Other diagnostic test Other diagnostic test – Semen analysis (SA) Semen analysis (SA) – USG USG

Treatment Treatment – Operation Operation – ART.: IUI, IVF, ICSI ART.: IUI, IVF, ICSI

Diagnostic and therapeutic Diagnostic and therapeutic algorithm algorithm (male)(male)

Sperm analysis

O, A, T, OA, OT, TA, OAT

grave O, A, T, OA, OT, TA, OAT

azoospermia

Testicular cells?

TESE, MESA

Treatment: operation, CC, hMG (FSH)

ICSI

IUI

Sperm analysis- Sperm analysis- recommendation by recommendation by WHOWHO

– General male infertility diagnostic test- General male infertility diagnostic test- SASA

– sterility sterility – sample should be delivered to sample should be delivered to

laboratory in 60 min. after ejaculation laboratory in 60 min. after ejaculation – abstinence min. 48 hours max. 7 days abstinence min. 48 hours max. 7 days – the next semen analysis between 7 the next semen analysis between 7

days and 3 months days and 3 months

Seminal quality, Seminal quality, cytology and sperm cytology and sperm quantitationquantitation

– liquefactioliquefactionn

– viscosity viscosity – volumevolume– colorcolor– pHpH– smellsmell

– Sperm count Sperm count – Sperm motion analysis Sperm motion analysis – WBC count (pyospermia) WBC count (pyospermia) – Spermatozoa count Spermatozoa count – Antisperm antibodies Antisperm antibodies – Sperm morphology Sperm morphology – Microbiology Microbiology

Semen analysisSemen analysis

– Microscope Microscope – Makler counting chamber Makler counting chamber – Immunobead test (IgG, IgA or IgM)Immunobead test (IgG, IgA or IgM)

– CASA CASA (computer-assisted sperm analysis)(computer-assisted sperm analysis)

Sperm motion analysisSperm motion analysis

1- immotile 1- immotile 2- weak movement with no forward 2- weak movement with no forward

progression progression 3- forward progression3- forward progression4- rapid forward progression; vigorous tail 4- rapid forward progression; vigorous tail

movement movement

Seminal quality- rangesSeminal quality- ranges

– Liquefaction < 60 minutes Liquefaction < 60 minutes – Volume > 2 ml Volume > 2 ml – Color- gray to white Color- gray to white

opalescent fluid opalescent fluid – pH 7,2 – 8,0pH 7,2 – 8,0

IMMUNOBEAD TESTIMMUNOBEAD TEST

Microscopic polyacrylamide Microscopic polyacrylamide spheres, ranging in size from 2 to spheres, ranging in size from 2 to 10 um, coated with anti-human 10 um, coated with anti-human immunoglobins against human IgG, immunoglobins against human IgG, IgA or IgMIgA or IgM

Normal sperm rangeNormal sperm range

Motility Motility >50% 3 or 2 ; or >50% 3 or 2 ; or >25% 3>25% 3

Sperm count Sperm count >20>20··101066/ml/ml WBC count WBC count <10<1066/ml/ml Spermatogonia Spermatogonia <5<5··101066/ml/ml Autoagglutinating Autoagglutinating <10%<10% Immunebead testImmunebead test <10%<10% Sperm morphology Sperm morphology >30% normal forms >30% normal forms

(WHO); 5-14% strict criteria (Kruger)(WHO); 5-14% strict criteria (Kruger)

Definitions of „abnormal” Definitions of „abnormal” countscounts

NormozoospermiaNormozoospermia Oligozoospermia Oligozoospermia << 2020··101066/ml/ml AstenozoospermiaAstenozoospermia <50% 3 or 2 ; or <50% 3 or 2 ; or

<25% 3<25% 3 TeratozoospermiaTeratozoospermia <30% <30% Azoospermia Azoospermia no sperm no sperm

Assisted Reproductive Assisted Reproductive TechniquesTechniques

IUI IUI (intrauterine (intrauterine insemination)insemination) AIH AIH (artificial insemination (artificial insemination by husband)by husband)AID AID (artificial insemination (artificial insemination by donor)by donor)

GIFTGIFT (gamet intrafallopian (gamet intrafallopian transfer)transfer)

IVF IVF (in vitro fertilization)(in vitro fertilization)ZIFT ZIFT (zygote intrafallopian (zygote intrafallopian transfer)transfer)PROST PROST (pronuclear stage (pronuclear stage intrafallopian transfer)intrafallopian transfer)IVF-ET IVF-ET (in vitro fertilization and (in vitro fertilization and embryo transfer)embryo transfer) ICSI ICSI (intracytoplasmic sperm (intracytoplasmic sperm injection)injection)

Indications to IUIIndications to IUI

Cervical factorCervical factor Chronic anovulation (COH-PCOS) Chronic anovulation (COH-PCOS) Male factorMale factor Immunologic disordersImmunologic disorders EndometriosisEndometriosis Idiopatic infertilityIdiopatic infertility

IUIIUI

ProceedingProceeding- Ovulation stimulation - Ovulation stimulation

- Sperm preparation (>1-4- Sperm preparation (>1-4··101066/ml)/ml)

- Artificial insemination- Artificial insemination Efficacy Efficacy (depended on indications and (depended on indications and

stimulation protocol)stimulation protocol)

– 10 – 30% pregnancies per cycle10 – 30% pregnancies per cycle– 40 – 60% accumulated 40 – 60% accumulated no improvement no improvement

after 4 cycles after 4 cycles

CONCLUSION: unjustified more than 4 correct IUI

Sperm preparation Sperm preparation (IUI, (IUI, IVF)IVF)gradientgradient

Sperm liquefaction Sperm liquefaction

Prepare the „gradient”Prepare the „gradient”

Stratification on gradientStratification on gradient

Centrifugation Centrifugation

Again centrifugation in Again centrifugation in EBSS EBSS

ARTART

semen

12

3

semen

40%Silica

80%Silica

Ovulation stimulation for Ovulation stimulation for IUIIUI

Clomiphene citrateClomiphene citrate– 50 – 250 mg p.o., day 5-9 50 – 250 mg p.o., day 5-9

Clomiphene citrate + hMG (FSH)Clomiphene citrate + hMG (FSH)– 50 – 250 mg p.o., day 5-9 50 – 250 mg p.o., day 5-9 – 75 IU from day 975 IU from day 9

hMG (FSH)hMG (FSH)– 75 – 150 IU from day (3) 575 – 150 IU from day (3) 5

AimAim– growth 1-3 follicles to 18mm. When Egrowth 1-3 follicles to 18mm. When E22 250–300 250–300

pg/ml/follicle pg/ml/follicle 10.000IU hCG 10.000IU hCG is administered to is administered to cause ovulationcause ovulation

Basic indications to Basic indications to IVFIVF Partial or complete tubal Partial or complete tubal

obliterationobliteration Chronic anovulation (COH-PCOS) Chronic anovulation (COH-PCOS) Male factorMale factor Immunologic disordersImmunologic disorders EndometriosisEndometriosis Idiopatic infertilityIdiopatic infertility

Indications to ICSIIndications to ICSI

Indications to ICSI Indications to ICSI with sperm from with sperm from ejaculateejaculate O, A, T, OATO, A, T, OAT

<1-4<1-4··101066/ml/ml after preparationafter preparation<5% <5% normalnormal forms forms

failure of classic IVFfailure of classic IVF (no fertilization)(no fertilization) Indications to MESAIndications to MESA

azoospermiaazoospermia (obstruction of ejaculatory (obstruction of ejaculatory ducts- ducts- obstructive azoospermiaobstructive azoospermia))

Indications to TESEIndications to TESEazoospermiaazoospermia (patency of ejaculatory (patency of ejaculatory

ducts- ducts- nonobstructive azoospermianonobstructive azoospermia))

IVF-ETIVF-ET (classic)(classic)

Ovulation stimulation Ovulation stimulation Sperm preparationSperm preparation Collecting the oocytes (under ultrasound control)Collecting the oocytes (under ultrasound control) Oocytes maturity Oocytes maturity assessmentassessment Oocytes inseminationOocytes insemination Fertilization assessment (16-24h)Fertilization assessment (16-24h) Embryo culture to Embryo culture to 4 (48h) - 8 (72h) 4 (48h) - 8 (72h)

blastomerblastomers stages stage or to blastocyst stageor to blastocyst stage ((120h)120h) Embryo transfer (ET)Embryo transfer (ET) Embryo cryopreservationEmbryo cryopreservation

ICSICSII

Ovulation stimulation Ovulation stimulation Sperm preparationSperm preparation Collecting the oocytes (under ultrasound Collecting the oocytes (under ultrasound

control)control) Oocytes maturity Oocytes maturity assessmentassessment Intracytoplasmic sperm injectionIntracytoplasmic sperm injection Fertilization assessment (16-24h)Fertilization assessment (16-24h) Embryo culture to Embryo culture to 4 (48h) - 8 (72h) blastomer4 (48h) - 8 (72h) blastomers s

stagestage or to blastocyst stageor to blastocyst stage ((120h)120h) Embryo transfer (ET)Embryo transfer (ET) Embryo cryopreservationEmbryo cryopreservation

Ovulation stimulation for Ovulation stimulation for IVF IVF (COH – controlled ovarian (COH – controlled ovarian hyperstimulation)hyperstimulation)

Short protocoł Short protocoł aGnRH from day 1aGnRH from day 1 hMG (FSH) 150–300IU from day 3 hMG (FSH) 150–300IU from day 3

Long protocoł Long protocoł aGnRH from day 20 aGnRH from day 20 previousprevious cycle cyclehMG (FSH) 150–300 IU from day 3 hMG (FSH) 150–300 IU from day 3

AimAimgrowth some follicles. When dominant follicle is growth some follicles. When dominant follicle is >18mm and 2 other at least 16 mm and E2 >18mm and 2 other at least 16 mm and E2 >1000pg/ml but>1000pg/ml but <5000pg/ml (OHSS risk) <5000pg/ml (OHSS risk), , 10.000IU hCG is administered to cause oocytes 10.000IU hCG is administered to cause oocytes maturity)maturity)

IVF - ICSI IVF - ICSI (skuteczność)(skuteczność)

IVFIVF ICSIICSI ICSI ICSI MESAMESA

ICSI ICSI TESETESE

FertilizationFertilizationss 50%50% 65%65% 60%60% 55%55%

Cells Cells divisionsdivisions 90%90% 95%95%

PregnanciePregnancies per cycles per cycle 15-25%15-25% 25-35%25-35% 35-45%35-45% 25-35%25-35%

IVF - ICSI IVF - ICSI ((eeffectiveness))

Implantation percentage when 1 Implantation percentage when 1 embryo is transferred in stage 4 – embryo is transferred in stage 4 – 8 blastomers is 12,5 – 17,5%8 blastomers is 12,5 – 17,5%

About 60% of embryos goes to About 60% of embryos goes to stage of 4 blastomers (and far?)stage of 4 blastomers (and far?)

Pregnancies percentage per cycle Pregnancies percentage per cycle (patients (patients << 40) 40)

– Less than 7 oocytesLess than 7 oocytes - 13%- 13%– More than 7 oocytes More than 7 oocytes - -

29%29%

Effectiveness of 1 mikrosurgery is equal with cumulative efficacy of 5 IVF trials

CryopreservationCryopreservation Freezing and storage Freezing and storage

– EmbryosEmbryos Stage 2 pronucleus Stage 2 pronucleus Stage 2-4 blastomersStage 2-4 blastomers Stage blastocystStage blastocyst

– Oocytes and ovarian tissueOocytes and ovarian tissue Benefits Benefits

– Low cost, no OHSS, possibility of more Low cost, no OHSS, possibility of more „aggresive” ovulation stimulation in first „aggresive” ovulation stimulation in first cyclecycle

Effectiveness

- 10 – 20% pregnancies per cycle- 10 – 20% pregnancies per cycle

Preparation to cryo-ETPreparation to cryo-ET

Natural cycle (indication is growth the Natural cycle (indication is growth the ovarian follicle) ovarian follicle) alternatively supplement therapy with alternatively supplement therapy with estrogens and progestagensestrogens and progestagens

Controlled cycle aGnRH with Controlled cycle aGnRH with supplement estrogens and supplement estrogens and progestagens therapyprogestagens therapy

Complications and Complications and potential risk of ARTpotential risk of ART

ComplicationsComplications– OHSSOHSS

Rare cardio- pulmonary failure, renal failure, DIC Rare cardio- pulmonary failure, renal failure, DIC ... ...

– Multiple pregnancy (5 – 40% !) Multiple pregnancy (5 – 40% !) Prematurity and preterm Prematurity and preterm labourslabours (to 98%), PIH (to 98%), PIH

(25%), bleeding (35%), anemia (15%), (25%), bleeding (35%), anemia (15%), isthmocervical insufficiency (15%) isthmocervical insufficiency (15%)

Strategies:

Transfer of 1-2 embryos; multiembryo transfer and consecutive embrioreduction or leaving this problem for obstetricians and neonatologists

Complications and Complications and potential risk of ARTpotential risk of ART

PotenPotential risktial risk– Ovarian cancerOvarian cancer

Increased risk of serous carcinomasIncreased risk of serous carcinomas, , low malignancylow malignancy ((high gradehigh grade))

More frequent after More frequent after Clomiphene citrateClomiphene citrate No confirmation in large No confirmation in large randomised randomised clinical trialsclinical trials !!! !!!

– TTheoretical risk of hormonosensitive neoplasm (breastheoretical risk of hormonosensitive neoplasm (breast, , endometrium)endometrium)

– GGeneteneticic defe defects transfercts transfer Male infertilityMale infertility (AZF, delY...) (AZF, delY...) Besides no risk of malformations was confirmedBesides no risk of malformations was confirmed ( (but too but too

short observationsshort observations) ) – 2,2–2,7%– 2,2–2,7%

IVM & IVCIVM & IVC

IVM IVM (in vitro maturation)(in vitro maturation)– OHSSOHSS prevention prevention– IIn vitro culture n vitro culture of ovarian follicles fromof ovarian follicles from antral antral to developed to developed

folliclefollicle– IVF – IVC – ET – IVF – IVC – ET

Multiple pregnancy preventionMultiple pregnancy prevention- IVC - IVC (in (in vitro culture)vitro culture)– IIn vitro culture n vitro culture of embryos to of embryos to blastocystblastocyst stage stage ( (the best the best

one forone for implanta implantationtion) – 40-60% ) – 40-60% of pregnanciesof pregnancies (blastocyst – (blastocyst –sesequential quential media) media) when compare towhen compare to 12,5 – 17,5% ( 12,5 – 17,5% (embryo embryo in the stage ofin the stage of 2-4-8 blastomer 2-4-8 blastomerss) )

– Culture the embryos to this stage make some problemsCulture the embryos to this stage make some problems. . AboutAbout 35-60% 35-60% of embryos in vitro goes to of embryos in vitro goes to blastocyst blastocyst stage stage. .

– IVCIVC gives the possibility gives the possibility of reliable evaluation the embryos of reliable evaluation the embryos quality. quality.

Preimplantation Preimplantation diagnosticdiagnostic

IndicationsIndications Age > 35 (?)Age > 35 (?) Previous child with chromosome abnormalities Previous child with chromosome abnormalities Carrier of genetic defectsCarrier of genetic defects

– Aneploidies (e.g. Down syndrome)Aneploidies (e.g. Down syndrome)– Monogenic disorders (np. fibrocystic disease)Monogenic disorders (np. fibrocystic disease)– X-linked inheritance (hemophilia) X-linked inheritance (hemophilia) (important child sex)(important child sex)

SamplingSampling– Blastomers biopsyBlastomers biopsy

MethodsMethods– PCR PCR (polymerase chain reaction)(polymerase chain reaction)

– FISH FISH (fluorescent in-situ hybridization)(fluorescent in-situ hybridization)

Conditions to start ARTConditions to start ART

IUIIUI– WomanWoman

Vaginal Vaginal bacteriological bacteriological examination examination

– ManMan 3-7 days of sexual 3-7 days of sexual

abstinenceabstinence

IVFIVF– WomanWoman

Vaginal bacteriological Vaginal bacteriological examinationexamination

hormonal profile hormonal profile Cervical canal explore with a Cervical canal explore with a

probe (?)probe (?) Hysteroscopy (?)Hysteroscopy (?)

– ManMan 3-7 days of sexual abstinence 3-7 days of sexual abstinence Sperm bacteriological examination Sperm bacteriological examination

prophylactic antibiotic therapyprophylactic antibiotic therapy (?)(?)