1. ART PREGNANCY COMPLICATIONS Prof. Aboubakr Elnashar Benha university hospital, Egypt elnashar53@hotmail.com
Aboubakr Elnashar

2. Complications of ART I. COMPLICATIONS OF OVULATION INDUCTION II. COMPLICATIONS OF OR III. ART PREGNANCY COMPLICATIONS IV. PSYCHOLOGICAL COMPLICATIONS
Aboubakr Elnashar

3. •At every stage of ART: There is a potential for complications some are dangerous& may be life threatening.
•Role of reproductive medicine clinicians: 1. Prevention of these complications 2. Establish the critical balance between efficacy and safety of ART.
Aboubakr Elnashar

4. INCIDENCE
•OHSS& OR complications: 1.3 %
•4 major clinical complications: 2% Severe& moderate OHSS Adnexal torsion OR complications Ectopic pregnancy.
Aboubakr Elnashar

5. All TT cycles
First TT cycle
Complication/1000 women
35
19
OHSS
2.5
1
Bleeding
11
5
Infection
93
42
Miscarriage
21
9.5
Ectopic
2
1
Other
5
2.5
Total
Aboubakr Elnashar

6. ART PREGNANCY COMPLICATIONS
Aboubakr Elnashar

7. Maternal
I.First-trimester bleeding
II.Miscarriage
III.Ectopic Pregnancy
IV.Heterotopic Pregnancy
V.PIH, gestational DM, CS
VI.Placenta previa
VII.PTL
Foetal
I.Molar Pregnancy
II.Multiple Pregnancy
III. Congenital Abnormality
Aboubakr Elnashar

8. A. Maternal I. First-trimester bleeding Incidence: 29 -36.2% Cause: A correlation was found with the number of embryos transferred. Consequence:
1.Increased 2nd trimester& 3rd trimester bleeding
2.PROM
3.Preterm contractions & PTL
4.NICU admissions
Aboubakr Elnashar

9. II. Miscarriage Rate: 15–23% Causes: 1. Fertilization of postmature ova 2. Luteal phase defect 3. Adverse effects of handling the oocytes 4. False higher rate when compared to G population: a. Different definitions of miscarriage, b. Use of highly sensitive assays for b-hCG, c. Close monitoring d. knowledge that the embryos were transferred on a particular day.
Aboubakr Elnashar

10. III. Ectopic Pregnancy Rate: 2 – 5% Tubal factor: 11%, Endometriosis: 2% Unexplained infertility: 3.5% IVF: 2.8% ICSI:1.3% Within the IVF group, EP was inversely correlated with maternal age.
Aboubakr Elnashar

11. Causes: -The most significant risk factor: Tubal pathology. -Non significant factors: Type of ovarian stimulation E2 level knee-chest or Lithotomy position at ET Number of embryos transferred
Aboubakr Elnashar

12. Possible Factors Associated with Ectopic Pregnancy in IVF
Means of Prevention
Tubal disease, hydrosalpinx
Pre-IVF salpingectomy or tubal occlusion
ET: 1 Depth
Mid-fundal transfer, ultrasound- guided transfer (controversial)
2 Amount of media used
15–20 μL of media
3 Number of embryos
Reduced or single-embryo transfer
4 Day 3 versus day 5
Controversial; some data suggest fewer ectopics with day 5 transfer
Aboubakr Elnashar

13. Sites:
1.Tubal
2.Bilateral tubal
3.Intramural
4.Ovarian
5.Abdominal
6.Cervical {reflux of embryos into the cervix after transfer or trauma to the cervix during ET}.
Aboubakr Elnashar

14. Diagnosis:
•Highly sensitive ß-hCG assay& TVS
•The usual algorithms may not apply in ART {more than one embryo usually is transferred, affecting ß-hCG level}. Marcus et al: 3ß-hCG levels& D13 progesterone combined with a history of PID: predictive value of 90 % Mol et al: D9 ß-hCG, after ET of >18 IU/L: EP is only 1%: expectant management (in an asymptomatic patient)
Aboubakr Elnashar

15. Prevention: Prophylactic salpingectomy: Treat more than 89 %of patients Disadvantages:
1.Removes any chance of normal spontaneous pregnancy
2.Not prevent interstitial pregnancies.
Aboubakr Elnashar

16. IV. Heterotopic Pregnancy
Rate:
Spontaneous pregnancies:1 in 2,600 to 1 in 30,000
ART: 1 in 100 pregnancies.
Recent reviews: 1-3 in 1000 pregnacies
% Spontaneous Pregnancies
% IVF Clinical Pregnancies
1.3
2.2
Ectopic pregnancy
0.07
0.5
Heterotopic pregnancy
Aboubakr Elnashar

17. Cause:
Multiple ovulations& multiple ET in a population with tubal or pelvic disease. Transfer of >4 embryos: increase risk
The technique of ET (volume& viscosity of medium, deep or superficial insertion of the catheter, and the degree of difficulty): inadequate data to draw firm conclusions.
Aboubakr Elnashar

18. Risk Delayed diagnosis: rupture, hage Diagnosis TVS Treatment:
1.Laparoscopic removal
2.TVS guided instillation of hyperosmolar glucose into the ectopic gestational sac
3.Potassium chloride injection with aspiration of the tubal sac
Aboubakr Elnashar

19. V. PIH, gestational DM, CS
•Are increased PIH: IVF Vs Non IVF: (15 Vs 4%) IUFD: 2%
•Reubinoff et al. only found increased risk of: CS
Aboubakr Elnashar

20. VI. Placenta previa Rate: 3-6 folds higher in singleton pregnancies compared with naturally conceived pregnancies. Cause: Women with pregnancies conceived after ART:
1.Older
2.More often primiparous.
3.More likely to have a multiple pregnancy.
Aboubakr Elnashar

21. VII. PTL PTL: Overall: 21.5-37% of births Singletons: 5.5–13.0% Low birth weight (<2,500 g): Overall: 30.5–37.5% all births Singletons: 7.7–11.0%
Aboubakr Elnashar

22. B. Foetal I. Molar Pregnancy Incidence: Difficult to be assessed. Causes:
1.Use of immature ova after ovulation induction
2.Disruption of meiosis& loss of maternal chromosomes {oocyte handling or degeneration}: increase the risk of complete mole.
3.Postmature oocytes are more prone to polyspermy: heterozygous complete or partial molar pregnancy.
Aboubakr Elnashar

23. Prevention: Modern molecular biology techniques PGD ICSI
Aboubakr Elnashar

24. II. Multiple Pregnancy
WHO recognized MP as a major complication of ART.
Rate:
In natural conception: 1 in 80 pregnancies
In ART: 1 in 50 , even in countries where the number of ET is limited to 3 embryos.
In ESHRE report 2006:
Singleton: 75.5%
Twin 23.2%,
Triplet 1.3%
Causes:
Ovulation stimulation drugs
Aboubakr Elnashar

25. Adverse outcomes:
1.Prematurity: short-term& long-term sequelae.
2.Neonatal mortality: 4 times as great among twins as it is among singletons
3.Long-term disability e.g. cerebral palsy: increased.
4.Stress associated with rearing children
5.Cost of prenatal& neonatal intensive care: increased
Aboubakr Elnashar

26. Prevention: ART success rate should be measured as a singleton live birth rate& not as PR 1- Elective double ET : Most European countries: reduced triplets& HOMP but has had no impact on twin pregnancies 2-Elective single ET: If significant risk of multiple gestation: relatively young, first or second IVF cycles, number of good-quality embryos.
Aboubakr Elnashar

27. •ESET: Reduces: multiple pregnancy & live birth in a fresh IVF cycle.
•<36 y ESET if needed, one frozen-and-thawed embryo Reduces: multiple births live births: not substantially lower than the rate that is achievable with a double ET.
Aboubakr Elnashar

28. 3. Individualize protocols: based on their risk of MP. 4-Multifetal pregnancy reduction (MFPR) Disadvantages
does not address the problem of twins.
ethical dilemma
psychological trauma It should never be considered as a standard line for prevention of MP and HOMP. It is only a rescue if other methods fail in the prevention
Aboubakr Elnashar

29. 5-Health education of couples& the society on the hazards of MP&HOMP 6-Convince reproductive medicine physicians -Obstetrical, neonatal, developmental& financial consequences -Measure of performance of ART is cumulative live birth per patient not pregnancy rate per cycle 7-Convince policymakers consequences of MP particularly cost
Aboubakr Elnashar

30. III. Congenital Abnormality 1. General: Types a. Major birth defects: NTD, esophageal atresias, omphalocele, hypospadias, cardiac septal defects
•Incidence
•little risk
•2 fold excess
•No higher rate of malformation in ICSI children than in IVF or naturally conceived children (large and reliable surveys) Explanation: -Increased maternal age. -During IVF: embryo is exposed to mechanical, thermal& chemical alterations.
Aboubakr Elnashar

31. b. Chromosomal anomalies Slightly increased in ICSI Predominantly sex chromosomes
Aboubakr Elnashar

32. c. Imprinting disorders
•Due to errors in imprinting, a process by which certain genes from either the mother or father are normally switched off.
•e.g. Beckwith-Wiedemann syndrome (large tongue, organs, and body size) Angelman syndrome (a neurological disorder once known as ‘‘happy puppet__ because of the child_s sunny outlook and jerky movements).
•Evidence is suggestive but not sufficient
Aboubakr Elnashar

33. 2. ICSI for patients with azoospermia {increased chromosomal aneuploidy rate}:
•Ludigs: No additional risk of major malformations in children testicular spermatozoa: 9% ejaculated spermatozoa: 8.4%
Aboubakr Elnashar

34. 3. Cryopreservation of embryos
•{Cellular changes in cryopreservation& thawing}
•Rates of minor & major congenital malformation were normal, up to the age of 4 ys
Aboubakr Elnashar

35. 4. Vetrification Outcome of vitrified oocytes reported fertilization rate: 92.9% PR: 32.5 IR /embryo:13.2% Babies born were healthy.
Aboubakr Elnashar

36. Prevention
1.Proper genetic counseling of the couple
2.Karyotyping of male partners before ICSI for severe oligoasthenospermia or NOA
3.Cystic fibrosis testing in both partners before ICSI for CAVD
4.PGD in some patients
Aboubakr Elnashar

37. IV. Stillbirth, perinatal mortality& infant mortality
•Higher {multiplicity& prematurity}..
•Case-control studies that account for confounding variables do not always confirm this.
•IVF/ ICSI Twins higher birth wt discordance more NICU admissions
Aboubakr Elnashar

38. Recommendations: SOGC2014 Outcomes Associated with Untreated Infertility infertility is an independent risk factor for obstetrical complications and adverse perinatal outcomes, even without the addition of ART. (II-2)
Aboubakr Elnashar

39. Outcomes Associated with Male Factor Infertility All men with severe oligozoospermia or azoospermia (sperm count <5 million/hpf) should be offered genetic/clinical counselling, karyotype assessment for chromosomal abnormalities, and Y-chromosome microdeletion testing prior to ICSI. (II-2A) All men with unexplained obstructive azoospermia should be offered genetic/clinical counseling and genetic testing for cystic fibrosis prior to ICSI. (II-2A)
Aboubakr Elnashar

40. Obstetrical, Perinatal, and Long-Term Outcomes Associated with ART Multiple Pregnancy and Adverse Obstetrical and Perinatal Outcomes Multiple pregnancy is the most powerful predictive factor for adverse maternal, obstetrical, and perinatal outcomes. Couples should be thoroughly counselled about the significant risks of multiple pregnancies associated with all assisted human reproductive treatments. (II-2A) The benefits and cumulative pregnancy rates of elective single embryo transfer (eSET) support a policy of using this protocol in couples with good prognosis for success, and eSET should be strongly encouraged in this population. (II- 2A) To reduce the incidence of multiple pregnancy, health care policies that support public funding for AHR, with regulations promoting best practice regarding eSET, should be strongly encouraged. (II-2A)
Aboubakr Elnashar

41. Singleton Pregnancies and Perinatal Outcome/Preterm Birth/Low Birth Weight Among singleton pregnancies, assisted reproductive technology (ART) is associated with increased risks of preterm birth and low birth weight infants, and ovulation induction (OI) is associated with an increased risk of low birth weight infants. Until sufficient research has clarified the independent roles of infertility and treatment for infertility, couples should be counselled about the risks associated with treatment. (II-2B) There is a role for closer obstetric surveillance for women who conceive with AHR. (III- L)
Aboubakr Elnashar

42. There is growing evidence that pregnancy outcomes are better for cryopreserved embryos fertilized in vitro than for FET. This finding supports a policy of eSET for women with a good prognosis (with subsequent use of cryopreserved embryos as necessary), and may reassure women who are considering IVF. (II-2A) Women and couples considering AHR and concerned about perinatal outcomes in singleton pregnancies should be advised that (1) ICSI does not appear to confer increased adverse perinatal or maternal risk over standard IVF, and (2) the use of donor oocytes increases successful pregnancy rates in selected women, but even when accounting for maternal age, can increase the risk of low birth weight and preeclampsia. (II-2B)
Aboubakr Elnashar

43. Fetal Structural, Chromosomal, and Imprinting Abnormalities Associated with Assisted Human Reproduction Structural Abnormalities (Malformations, Deformations, and Disruptions) Any ART procedure should be prefaced by a discussion of fetal outcomes and the slight increase in the risk of congenital structural abnormalities, with emphasis on known confounding factors such as infertility and body mass index. (II-2B) In pregnancies achieved by ART, routine anatomic ultrasound for congenital structural abnormalities is recommended between 18 and 22 weeks. (II-2A)
Aboubakr Elnashar

44. Chromosomal Disorders Pregnancies conceived by ISCI may be at increased risk of chromosomal aberrations, including sex chromosome abnormalities. Diagnostic testing should be offered after appropriate counselling. (II-2A) Imprinting Disorders The relative risk for an imprinting phenotype such as Silver-Russell syndrome, Beckwith-Wiedemann syndrome, or Angelman syndrome is increased in the assisted reproduction population, but the actual risk for one of these phenotypes to occur in an assisted pregnancy is estimated to be low, at less than 1 in 5000. The exact biological etiology for this imprinting risk increase is likely heterogeneous and requires more research. (II-2)
Aboubakr Elnashar

45. The possible increased risk for late onset cancer due to gene dysregulation for tumour suppression requires more long-term follow-up before the true risk can be determined. (III-A) Preimplantation Genetic Screening The clinical application of preimplantation genetic testing in fertile couples must balance the benefits of avoiding disease transmission with the medical risks and financial burden of IVF. (III-B) Preimplantation screening for aneuploidy is associated with inconsistent findings for improving pregnancy outcomes. Any discussion of PGS with patients should clarify that there is no adequate information on the long-term effect of embryo single cell biopsy. (I-C)
Aboubakr Elnashar

46. Guidelines for Reducing Complications of ART General Measures to reduce risk
1.BMI
2.Blood tests
3.Kidney function tests
4.Liver function tests
5.Blood sugar
6.FSH and E2
7.Abdominal and pelvic US
8.In selected patients: ECG Mammography Salpingectomy Hysteroscopy
Aboubakr Elnashar

47. Pregnancy complications
1.Uterine cavity empty with positive BHCC: exclude ectopic and heterotopic pregnancies
2.Health education of patients on risks of MP
3.Single embryo transfer in selected patients
4.Multifetal pregnancy reduction for HOMP
Aboubakr Elnashar

48. Congenital of abnormalities
1.Proper genetic counseling of the couple
2.Karyotyping of male partners before ICSI for severe oligoasthenospermia or NOA
3.Cystic fibrosis testing in both partners before ICSI for CAVD
4.PGD in some patients
Aboubakr Elnashar

49. Thanks
Aboubakr Elnashar
Aboubakr Elnashar