Dr ForuhanDr Foruhan

مرکز باروری وناباروری اصفهان مرکز باروری وناباروری اصفهان

Isfahan Fertility& Isfahan Fertility& Infertility CenterInfertility Center

COMPLICATIONS OF ASSISTED COMPLICATIONS OF ASSISTED REPRODUCTIVE TECHNOLOGY REPRODUCTIVE TECHNOLOGY

(ART)(ART)

با سیسیدر در ناباروري درمان گذشته با سال ناباروري درمان گذشته سالهاي هاي روش . ARTARTروش است شده . متحول است شده متحول

بارداري در وتاخير ازدواج سن رفتن بارداري باال در وتاخير ازدواج سن رفتن باالبه به نياز نتيجه artartنياز ودر افزايش نتيجه را ودر افزايش را

بخصوص آنرا بخصوص مخاطرات آنرا افرايش hsshssمخاطرات افرايش را رادهد . دهد .مي مي

ARTARTمخاطرات مخاطرات شامل خود كه درمان به شامل مربوط خود كه درمان به Drug relatedDrug relatedمربوط

دارو : دارو : الف الفها: ب ب تخمدان از تخمك آوري ها: جمع تخمدان از تخمك آوري Egg collectionsEgg collectionsجمع

درمان ج :ج : نتيجه به درمان مربوط نتيجه به outcomeoutcome مربوط

TreatmentTreatment Drug related Drug related

Local reactionLocal reaction At egg collectionAt egg collection

Ovarian hyper stimulationOvarian hyper stimulation TraumaTrauma HæmorrhageHæmorrhage InfectionInfection

Outcome Outcome Increased miscarriage rateIncreased miscarriage rate Increased multiple pregnancy Increased multiple pregnancy Increased prenatal mortality and morbidityIncreased prenatal mortality and morbidity Long term (Ovarian cancer)Long term (Ovarian cancer) Ovarian HSSOvarian HSS Potentially life threatening complication of Potentially life threatening complication of

abnormal physiologyabnormal physiology

ها گونادوتروپين اثر در بيشتر ها كه گونادوتروپين اثر در بيشتر كه

مي بوجود كلوميد مثل خوراكي داروهاي اثر در مي كمتر بوجود كلوميد مثل خوراكي داروهاي اثر در كمترآيد.آيد.

OHSS is systemic disease resulting from vasoactive OHSS is systemic disease resulting from vasoactive

products released by hyper stimulated ovaries .products released by hyper stimulated ovaries .

The pathophysiogy of OHSS is characterized by The pathophysiogy of OHSS is characterized by

increased capillary permeability:increased capillary permeability:

leading to leakage of fluid from the vascular leading to leakage of fluid from the vascular

compartment compartment

With third space fluid accumulation With third space fluid accumulation

Intravascular dehydrationIntravascular dehydration

SeverSever manifestations include manifestations include

A tendency to develop thrombosis A tendency to develop thrombosis

Renal and liver dysfunction Renal and liver dysfunction

Acute respiratory distress syndrome (ARDS) ,Acute respiratory distress syndrome (ARDS) ,

Causing serious morbidityCausing serious morbidity

Although the true incidence of mortality from Although the true incidence of mortality from

OHSS is unknownOHSS is unknown

Possibly under-reported ,deaths from OHSS Possibly under-reported ,deaths from OHSS

are rare are rare

The reported causes of death include ARDS The reported causes of death include ARDS

(two cases ) , cerebral infarction (two cases ) (two cases ) , cerebral infarction (two cases )

and hepatorenal failure in a woman wilh and hepatorenal failure in a woman wilh

pre-existing hepatitis ( one case).(RCOG)pre-existing hepatitis ( one case).(RCOG)

: :ممئئعالعال - - Gross ovarianGross ovarian enlargement enlargement - - AscitesAscites

- - Due to an increase in capillary PermeabilityDue to an increase in capillary Permeability

-Leakage of protein rich fluid from the -Leakage of protein rich fluid from the

intravascular space resulting in:intravascular space resulting in:

+ Hæmoconcentration+ Hæmoconcentration

+ Third space edema (usually ascites)+ Third space edema (usually ascites)

Less frequently Less frequently

+ Pleural and Pericardial effusions + Pleural and Pericardial effusions

Risk factors of OHSSRisk factors of OHSS Young ageYoung age

Low body weightLow body weight

Polycystic ovariesPolycystic ovaries

High dose gonadotrophinsHigh dose gonadotrophins

Large number of oocytes Large number of oocytes

High æstradiol level (on day of HCG administration)High æstradiol level (on day of HCG administration)

Use of HCG for luteal supportUse of HCG for luteal support

Ensuing PregnancyEnsuing Pregnancy

PathogenesisPathogenesis

Exact mechanism unknown. The most widely accepted hypothesis is:Exact mechanism unknown. The most widely accepted hypothesis is:

Increased capillary permeability leading toIncreased capillary permeability leading to

extravasations of fluid.extravasations of fluid.

First – in the ovaries First – in the ovaries

Then – Abdominal cavityThen – Abdominal cavity

Macroscopically:Macroscopically:

The ovaries are:The ovaries are:

LargeLarge

EdematousEdematous

Multiple cystic structuresMultiple cystic structures Areas of hæmorrhageAreas of hæmorrhageMicroscopically:Microscopically: +Multiple cystic hemorrhagic corpora lutea at +Multiple cystic hemorrhagic corpora lutea at

different stages of development.different stages of development. +Theca lutein cysts with stromal ædema and +Theca lutein cysts with stromal ædema and

hoemorrhagehoemorrhage علت براي موجود علت مدارك براي موجود Increased capillary Increased capillary((مدارك

permeabilitypermeability ( ( : از از :عبارتند عبارتند Immune systemImmune system Renin angiotensinRenin angiotensin Exaggerated follicular angiogenesisExaggerated follicular angiogenesis Possibly mediated by vascular endothelial Possibly mediated by vascular endothelial

growth factorgrowth factor

Clinical featuresClinical features

OHSS has two modes of presentationsOHSS has two modes of presentations:: A: early B:late A: early B:late

3-7 days after HCG 12-17Days after HCG 3-7 days after HCG 12-17Days after HCG

administrationadministration

The best predictors of:The best predictors of:

Early form areEarly form are

+ Number of oocytes retrieved+ Number of oocytes retrieved

+ serum estradiol levels on the day of HCG + serum estradiol levels on the day of HCG

administrationadministration

The late form is more related to: The late form is more related to:

+ Pregnancy + Pregnancy

+ Number of gestational sacs (Seen on + Number of gestational sacs (Seen on

ultrasound four weeks after HCG injection)ultrasound four weeks after HCG injection)

ClassificationThe most common is Golan classification

Grade 1Grade 1 : :

Abdominal distension and discomfortAbdominal distension and discomfort . .

Grade 2Grade 2 : : grade 1 plus nausea, vomiting and/or diarrhea; grade 1 plus nausea, vomiting and/or diarrhea; ovaries enlarged 5-12 cmovaries enlarged 5-12 cm..

Grade 3Grade 3: : Features of mild OHSS plus ultrasonic evidence of Features of mild OHSS plus ultrasonic evidence of ascitesascites . .

Grade 4Grade 4: : Features of moderate OHSS plus clinical ascites Features of moderate OHSS plus clinical ascites and/or hydrothorax with dyspnoeaand/or hydrothorax with dyspnoea . .

Grade 5Grade 5 : : Grade 4 plus decreased blood volume, increased Grade 4 plus decreased blood volume, increased blood viscosity, hypercoagulability, diminished blood viscosity, hypercoagulability, diminished

renal perfusion and functionrenal perfusion and function . .

Mild

Moderate

Severe

The most common is Golan classificationThe most common is Golan classification Mild Mild ModerateModerate Severe Severe In gonadotrophin stimulated ARTIn gonadotrophin stimulated ART Mild 23-33 % with minimal consequences Mild 23-33 % with minimal consequences Moderate 3-6 %Moderate 3-6 %

سال آمار اصفهان مركز سال در آمار اصفهان مركز به 13871387در منجر به كه منجر كهشده آسيت شده آسپراسيون آسيت سال% 5.75.7آسپراسيون ودر است سال% بوده ودر است 13881388بوده

به آمار به این آمار یافت% 4.674.67این یافت% کاهش کاهش

Sever 0.3 – 0.5 % (is life threatening requires Sever 0.3 – 0.5 % (is life threatening requires

intensive monitoring and expert management)intensive monitoring and expert management)

Classification

Typical presentationTypical presentationAbdominal painAbdominal painDistensionDistensionNauseaNauseaVomiting Vomiting Weight gainWeight gainDispneaDispneaClinical signs may include:Clinical signs may include: - Rapid weight gain- Rapid weight gain - Oliguria- Oliguria - Aneuria- Aneuria - Hæmoconcentration- Hæmoconcentration

•- Leucocytosis•-Electrolyte imbalance (Typically hyponatremia -

hyperkalemia)•Ascites •Pleural and pericardial effusion•Adult respiratory distress syndrome

( ARDS)•Hypercoagulability with•-thromboembolic sequels •-multiple organ failure •hypovolæmia•Hæmoconcentration•As a result of movement of fluids from the vascular

compartment to the third space resulting in :

Lower blood and central venous pressureLower blood and central venous pressure

If not conrrected leads to :If not conrrected leads to : Decreased renal perfusion Decreased renal perfusion Stimulating the renal tubules to increase salt and Stimulating the renal tubules to increase salt and

water reabsorption in the proximal tubules water reabsorption in the proximal tubules producing.producing.

Oliguria Oliguria (Lower urinary sodium excretion)(Lower urinary sodium excretion) As a resultAs a result Less sodium being presented to the distal tubulesLess sodium being presented to the distal tubules A decrease in the exchange of hydrogen and A decrease in the exchange of hydrogen and

potassium for sodium .potassium for sodium .

Hyperkalaemic acidosis Hyperkalaemic acidosis As the ascitic fluid is an exudate and therefore protein – As the ascitic fluid is an exudate and therefore protein –

rich rich Serum albumin – level decrease markedlySerum albumin – level decrease markedly Increased thrombogenesis Result from :Increased thrombogenesis Result from : Hæmoconcentration Hæmoconcentration Immobility Immobility Mechanical compression of venous blood flowMechanical compression of venous blood flow In the pelvic brimIn the pelvic brim Lower limbsLower limbs High estradiol level High estradiol level Endothelial cell damage from Stress induced Endothelial cell damage from Stress induced

leucocytosisleucocytosis * Arterial and venous thromboses occurs in upper and * Arterial and venous thromboses occurs in upper and

lower limbs as well as intracerebrally causing:lower limbs as well as intracerebrally causing: DVT andDVT and Hæmiparesis.Hæmiparesis.

CausingCausing

Pulmonary manifestations of OHSSPulmonary manifestations of OHSS

+ Pleural effusion (usually secondary + Pleural effusion (usually secondary

to the ascites and possibly similar in to the ascites and possibly similar in

pathogenesis to Meig`s Syndrome)pathogenesis to Meig`s Syndrome)

+ ARDS (in rare cases) + ARDS (in rare cases)

Death can occur especially if liver function Death can occur especially if liver function

is impaired (I in 500/000 stimulated cycles).is impaired (I in 500/000 stimulated cycles).

Clinical ManagementClinical Management

Clinical ManagementClinical Management No active management unless the condition progresses No active management unless the condition progresses Hospital admission is essential for all patients with severe Hospital admission is essential for all patients with severe

OHSS (Golan grade 4 and 5 ) OHSS (Golan grade 4 and 5 ) Requires:Requires: Complete physical examinationComplete physical examination AbdominalAbdominal PelvicPelvic Ultrasound (To detect presence of ascites)Ultrasound (To detect presence of ascites) Serum levels of:Serum levels of: NaNa KK Creatinine Creatinine AlbuminAlbumin HCTHCT

Criteria for admissionCriteria for admission

Criteria for admissionCriteria for admission NauseaNausea Abdominal pain causingAbdominal pain causing Intolerance of oral fluids Intolerance of oral fluids Tense distended abdomen with Tense distended abdomen with Ascites Ascites Any abnormal blood biochemistry Any abnormal blood biochemistry (Indications of development of grad 4-5 disease)(Indications of development of grad 4-5 disease) Grade 2-3 can be managed at home. Grade 2-3 can be managed at home.

از جلوگيري جهت حركت كاهش براي از پيشنهاد جلوگيري جهت حركت كاهش براي پيشنهاد

Ovarian torsionOvarian torsion كه باشيد داشته نظر در كه ولي باشيد داشته نظر در وليحركت حركت كاهش كاهش

. ميدهد افزايش را ترومبوآمبولي .خطر ميدهد افزايش را ترومبوآمبولي خطر

ها ها توصيه توصيه

) در ليتر يك حداقل زياد مايعات و آب در ( آشاميدن ليتر يك حداقل زياد مايعات و آب آشاميدنزياد روز )روز ) نه زياد ولي نه ولي

. نماند تشنه بیمار که .آنقدر نماند تشنه بیمار که آنقدر مقدار مقدار ثبت Output , IntakeOutput , Intake ثبت

Allowing women to drink according Allowing women to drink according to thirst represents the most to thirst represents the most physiological approach to replacing physiological approach to replacing volume .volume .

Output of less than 1000ml/day or a Output of less than 1000ml/day or a discrepancy of more than 1000 ml discrepancy of more than 1000 ml between input and output are between input and output are suggestive of renal compromise suggestive of renal compromise and severe OHSS requiring hospital and severe OHSS requiring hospital admission.admission.

Semi bed – rest Assessment Stabilization Vital Signs:PulseBlood pressureTemperatureRespiratory rate Abdominal girth (daily) Ultrasound (vaginal – abdominal) To assess ovarian size and ascites .Gentle abdominal and pelvic examination.Intravenous line Indwelling catheter if urinary output is less than 50 ml/hour.Full blood count.Electrolyte status Liver function tests Coagulation screen should be estimated daily

در بيمارستا

ن

In full blood pictureIn full blood picture Hæmatocrit (HCT) is the most important parameter, as it Hæmatocrit (HCT) is the most important parameter, as it

reflectsreflects Plasma volume changes.Plasma volume changes. * An elevated HCT correlates well with both severity of OHSS * An elevated HCT correlates well with both severity of OHSS

and individual response to treatment.and individual response to treatment. A HCT of more than 45 % is a serious warning sign.A HCT of more than 45 % is a serious warning sign. A HCT of more than 55 % signals life – threatening A HCT of more than 55 % signals life – threatening

situation. situation. While the degree of loukocytosis is representative of While the degree of loukocytosis is representative of

hæmoconcentration, it may also be caused by generalized hæmoconcentration, it may also be caused by generalized stress situations. stress situations.

Heparin Heparin Antiembolic stockings.Antiembolic stockings. Should be used as prophylaxis against DVT.Should be used as prophylaxis against DVT.

Only normal saline should be used at a rate of 150 ml/hour with a Only normal saline should be used at a rate of 150 ml/hour with a

rate to maintain.rate to maintain.

Urinary output at 30-50 ml/hour (minimum output representing Urinary output at 30-50 ml/hour (minimum output representing

adequate renl perfusion.) adequate renl perfusion.)

Fluids given in excess of this requirement will simply leak into the Fluids given in excess of this requirement will simply leak into the

abdominal cavity.abdominal cavity.

I.V. infusion I.V. infusion

To correct hypovolæmia To correct hypovolæmia

Restore renal perfusion and as a result urine production Restore renal perfusion and as a result urine production

In view of both hyponatræmia and hyperkalæmia.Which are In view of both hyponatræmia and hyperkalæmia.Which are

typical of the syndrometypical of the syndrome

Only normal saline should be used.Only normal saline should be used.

If serum albumin levels are <30 g/l the patient If serum albumin levels are <30 g/l the patient should be given 200ml of 20 % albumin should be given 200ml of 20 % albumin intravenously. intravenously.

This can be repeated depending on daily This can be repeated depending on daily fluctuations in serum volumes.fluctuations in serum volumes.

Remember that ascites is an exudate so a Remember that ascites is an exudate so a percentage of albumen infused will leak into percentage of albumen infused will leak into the peritoneal cavity drawing fluids after it. the peritoneal cavity drawing fluids after it.

In severe casesIn severe cases Dopamine Dopamine

Which has a vasodilator effect on renal Which has a vasodilator effect on renal arteries can be used to improve renal function arteries can be used to improve renal function by increasing renal blood flow. by increasing renal blood flow.

Diuretics areDiuretics are Contraindicated Contraindicated They induce a diuresis by removing fluids They induce a diuresis by removing fluids

from the intravenous compartment and have from the intravenous compartment and have no effect on the ascites or the course of no effect on the ascites or the course of disease.disease.

• If oliguria persists despite adequate If oliguria persists despite adequate intravascular volume expansion and a intravascular volume expansion and a normal intravenous pressure may have a normal intravenous pressure may have a role (with careful homodynamic role (with careful homodynamic monitoring )monitoring )

Surgical managementSurgical managementParacentesis :Paracentesis :Transabdominally Transabdominally Transvaginally Transvaginally Indicated for Indicated for Symptomatic relief of large volumes of ascites . Symptomatic relief of large volumes of ascites . In addition to the relief results in :In addition to the relief results in :Improved renal function.Improved renal function.Improved blood osmolarity Improved blood osmolarity hæmoconcentration hæmoconcentration Reduced pulmonary compromiseReduced pulmonary compromiseIt should be performed under ultrasound guidance becauseIt should be performed under ultrasound guidance becauseOf the risk to the ovaries and bowels.Of the risk to the ovaries and bowels.

Prevention of OHSSPrevention of OHSS Stop exogenous gonadotrophines Stop exogenous gonadotrophines Continue GnRh releasing hormone analogueContinue GnRh releasing hormone analogue Withold HCG ( E2 decrease to safer values ) Withold HCG ( E2 decrease to safer values ) Use progesterone for luteal - phase support not HCGUse progesterone for luteal - phase support not HCG Cryopreservation of all embryos Cryopreservation of all embryos Albumin infusion at the time of oocyte retrieval Albumin infusion at the time of oocyte retrieval Albumin infusion will:Albumin infusion will: A: increase oncotic pressure to help to Prevent ascites. A: increase oncotic pressure to help to Prevent ascites. B: to sequester vasoactive substances released from the B: to sequester vasoactive substances released from the

corpora lutea corpora lutea OHSS can also occur:OHSS can also occur: In association with ovulation induction with gonadotrophins In association with ovulation induction with gonadotrophins

(without IVF)(without IVF) And also with clomiphen only .And also with clomiphen only . A low dose step – up protocol for gonadotrophin minimizes the A low dose step – up protocol for gonadotrophin minimizes the

risk of overstimulation especially in PCOS.risk of overstimulation especially in PCOS.

Complications of oocyte retrievalComplications of oocyte retrieval.. By ultrasound (Vaginally)By ultrasound (Vaginally)

Rarely with laparoscopyRarely with laparoscopy HæmonhageHæmonhage Infection (PID)Infection (PID) injury to the ovary or injury to the ovary or Pelvic visceraPelvic viscera BowelsBowels Blood vesselsBlood vessels Adnæxal torsion Adnæxal torsion Appendicitis as a result of puncture hole in the Appendicitis as a result of puncture hole in the

appendix.appendix. IncidenceIncidence 14 cases out of 3656 (dicker et al 1993)14 cases out of 3656 (dicker et al 1993) 7 cases 2500 (Roast et al 1996 )7 cases 2500 (Roast et al 1996 )

Ovarian torsionOvarian torsion: : A rare complication of IVF A rare complication of IVF

increases increases WithWith Ovarian sizeOvarian size Softening of ligaments Softening of ligaments Overall risk one in 5000 stimulations.Overall risk one in 5000 stimulations. It is greater in the presence of OHSS.It is greater in the presence of OHSS. The characteristic symptoms include sudden, The characteristic symptoms include sudden,

extreme abdominal pain accompanied by extreme abdominal pain accompanied by nausea.nausea.

Early diagnosis and untwisting of the ovary at Early diagnosis and untwisting of the ovary at laparoscopy or laparatomy is essential and may laparoscopy or laparatomy is essential and may result in survival of the ovary.result in survival of the ovary.

Even if the ovary appear darkened on Even if the ovary appear darkened on examination.examination.

Long – term risks of ovarian cancerLong – term risks of ovarian cancer: ولي داد توان نمي مورد اين در قطعي ولي :جواب داد توان نمي مورد اين در قطعي جواب از بيش كسانيكه از در بيش كسانيكه كلوميفن 1212در با كلوميفن دوره با دوره

تومورهاي اند شده درمان تومورهاي سيترات اند شده درمان و و BorderlireBorderlire سيتراتinvasiveinvasive . شده شده . ديده ديده

براي فقط كلوميد انگلستان در حاضر حال براي در فقط كلوميد انگلستان در حاضر حال 66درولي ميشود توصيه ولي ماه ميشود توصيه مجاز 1212تا تا RCOGRCOGماه را مجاز ماه را ماه

ميداند.ميداند.

Long – term follow up studies are necessary to provide the answer to Long – term follow up studies are necessary to provide the answer to this matter. this matter.

و گذاري تخمك تحريك مابين اي رابطه آيا كه نيست مشخص و هنوز گذاري تخمك تحريك مابين اي رابطه آيا كه نيست مشخص هنوز؟" نه يا دارد وجود تخمدان كانسر پيدايش ؟" متعاقبا نه يا دارد وجود تخمدان كانسر پيدايش متعاقبا

Infertility and nulliparity are probably important confounding factors Infertility and nulliparity are probably important confounding factors while. while.

The combined oral contraceptive pill is thought to be protective for The combined oral contraceptive pill is thought to be protective for ovarian cancer by virtue of its inhibitory effect on ovulation. Many ovarian cancer by virtue of its inhibitory effect on ovulation. Many patients undergoing ovarian stimulations, with or without IVF are patients undergoing ovarian stimulations, with or without IVF are infertile as a direct result of ovulatory failure. infertile as a direct result of ovulatory failure.

Early pregnancy lossEarly pregnancy loss MiscarriageMiscarriage Ectopic pregnancy Ectopic pregnancy Miscarriage is divided intoMiscarriage is divided into:: A PreclinicalA Preclinical B Clinical B Clinical Preclinical : ends within 28 days of fertilization Preclinical : ends within 28 days of fertilization Clinical : spontanious termination of pregnancy Clinical : spontanious termination of pregnancy Where the menstrual period is delayed more than 14 daysWhere the menstrual period is delayed more than 14 days 29 % in IVF pregnancies. 29 % in IVF pregnancies. Cause:Cause: Gonadotrophin therapyGonadotrophin therapy Multiple ovulation Multiple ovulation PCOSPCOS

age related cases in chromosomal abnormality age related cases in chromosomal abnormality Length of time taken to conceiveLength of time taken to conceive The apparent increase in miscarriage associated with IVF The apparent increase in miscarriage associated with IVF

appears to be multifactorial with infertility itself, regardless of appears to be multifactorial with infertility itself, regardless of cause ,being of major significance. cause ,being of major significance.

Ectopic pregnancyEctopic pregnancy Varies between 2-11 % in reported series of IVF.In general Varies between 2-11 % in reported series of IVF.In general

population 2.5 % population 2.5 % Aetiology: is multi-factorialAetiology: is multi-factorial Tubal disease being the main factorTubal disease being the main factor Damaged tubes Damaged tubes Reverse migration, associated with high concentration of Reverse migration, associated with high concentration of

estradiol or an altered estrogen progesterone ratios. estradiol or an altered estrogen progesterone ratios. The number of embryos transferred The number of embryos transferred The technique of embryo transferThe technique of embryo transfer By forcing the embryo through the tube itself by hydrostatic By forcing the embryo through the tube itself by hydrostatic

presser due to:presser due to: + Large volume of transfer fluid + Large volume of transfer fluid + Or the transfer catheter to be placed beyond the mid + Or the transfer catheter to be placed beyond the mid

cavitycavity

Heterotopic pregnancy is estimated to Heterotopic pregnancy is estimated to occurr 1 % of IVF pregnancies occurr 1 % of IVF pregnancies

Compared with an incidence of one in four Compared with an incidence of one in four or 6 or 7000 spontaneous Pregnancies.or 6 or 7000 spontaneous Pregnancies.

A significant number are undetected. A significant number are undetected. Laparoscopic clipping of the proximal end Laparoscopic clipping of the proximal end

of a hydrosalpinx or salpingectomy would of a hydrosalpinx or salpingectomy would prevent the occurence of tubal prevent the occurence of tubal pregnancies in patients with pregnancies in patients with hydrosalpinges. hydrosalpinges.

At the Same time increase their chance of At the Same time increase their chance of a successful outcome with IVFa successful outcome with IVF. .

Obstetric outcomeObstetric outcome

The women who become pregnant with ART are at increased risks The women who become pregnant with ART are at increased risks

of: of:

multiple pregnancies multiple pregnancies

50 % UK50 % UK

32 % USA32 % USA

7 % Triplets and higher 7 % Triplets and higher

- Preterm delivery (5-6 fold increase <37 weeks and low birth - Preterm delivery (5-6 fold increase <37 weeks and low birth

- weight <2500g and 27 fold increase in multiple births) - weight <2500g and 27 fold increase in multiple births)

Perinatal mortality is increased Perinatal mortality is increased Seven fold among triplets Seven fold among triplets Five fold among twins Five fold among twins ThereforeTherefore Reducing the proportion of multiple Reducing the proportion of multiple

pregnancies among IVF conceptions pregnancies among IVF conceptions should contribute to a significant should contribute to a significant reduction in perinatal morbidity and reduction in perinatal morbidity and mortality. mortality.

Human fertilization and embryology Human fertilization and embryology authority (HFEA)authority (HFEA) guidelines.guidelines.

in Englandin England

Allow for the transfer of no more than three embryos. Allow for the transfer of no more than three embryos.

RCOG guidelines recommend that no more than two embryos be RCOG guidelines recommend that no more than two embryos be

transferred.transferred.

In In

Older womenOlder women

Patient with poor quality embryos transfer of 3 or more embryos Patient with poor quality embryos transfer of 3 or more embryos

increase the pregnancy rate without a significant increase in multiple increase the pregnancy rate without a significant increase in multiple

pregnancy .pregnancy .

In future transfer of single blastocyst with high In future transfer of single blastocyst with high potential and two blastocycts in others should help to potential and two blastocycts in others should help to reduce the increase in perinatal mortality and reduce the increase in perinatal mortality and morbidity from multiple pregnancies. morbidity from multiple pregnancies.

Perinatal mortality rate in ART even when matched for Perinatal mortality rate in ART even when matched for age , parity and fetal sex was more than twice that in age , parity and fetal sex was more than twice that in control pregnancies. (13.4 % VS , 5.9 % DHONT et al control pregnancies. (13.4 % VS , 5.9 % DHONT et al 1999 )1999 )

The incidence of congenital malformations was also The incidence of congenital malformations was also higher 3.1 % VS 1.7 % the general population.higher 3.1 % VS 1.7 % the general population.

This difference was lost after matching for age. This difference was lost after matching for age.

Psychological morbidityPsychological morbidity The nature of treatment in ART predisposes The nature of treatment in ART predisposes

to psychological stress: to psychological stress: The fact that treatment can fail at The fact that treatment can fail at

many different points:many different points: The cost of ampoules and procedure The cost of ampoules and procedure Stimulation and injectionsStimulation and injections Semen sample productionSemen sample production FertilizationFertilization TransferTransfer Implantation Implantation There is a constant level of apprehension. There is a constant level of apprehension. Waiting after transfer at least 2 weeks Waiting after transfer at least 2 weeks The result especially if failed.The result especially if failed.

اثرات درجه گيري اثرات اندازه درجه گيري روان ARTART اندازه و روح روان بر و روح برنيست پذير امكان نيست زوج پذير امكان .. زوج

درمان از درمان قبل از قبل درمان درمان حين حين درمان از درمان بعد از بعد شك شك بدون بدون There is long There is long –– term psychological morbidity term psychological morbidity

after treatment failure.after treatment failure. و دپرسيون ايجاد خود فرزندي بي ادامه شك و بي دپرسيون ايجاد خود فرزندي بي ادامه شك بي

بيمار براي را ياس و نوميدي و گناه بيمار احساس براي را ياس و نوميدي و گناه احساسداشت داشت خواهد .. خواهد

ConclusionConclusion

With continuing scientific advances in embryology,With continuing scientific advances in embryology,

Voluntary delaying of pregnancies Voluntary delaying of pregnancies

Demand for ART will continue to rise Demand for ART will continue to rise

The iatrogenic complications of ART includes.The iatrogenic complications of ART includes.

Potentially life threatening condition of OHSSPotentially life threatening condition of OHSS

Surgical complications of ART , Surgical complications of ART ,

Increased early pregnancy lossIncreased early pregnancy loss

Increased perinatal mortality due to : Increased perinatal mortality due to :

Multiple birthMultiple birth

Reduction in the number of embryos transfered and single blastocyst Reduction in the number of embryos transfered and single blastocyst

transfer .may improve perinatal mortality.transfer .may improve perinatal mortality.

ART especially ICSI has the potential for genetic abnormalities that are the ART especially ICSI has the potential for genetic abnormalities that are the

original cause of or are associated with a couple’s infertility. original cause of or are associated with a couple’s infertility.

The question of The question of

Whether there may be an associated increase in congenital Whether there may be an associated increase in congenital

abnormalities has not been completely resolved. abnormalities has not been completely resolved.

The psychological health of the couple is an area in which further The psychological health of the couple is an area in which further

investigation and evaluation are required. investigation and evaluation are required.

WOMEN AT RISK OF OHSSWOMEN AT RISK OF OHSS

What advice should women receive What advice should women receive about the risk of OHSSabout the risk of OHSS??