Multiple pregnancy in obstetrics and gynaecology

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1. WELCOME 1

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3. MULTIPLE PREGNANCY-TWINS 3

4. INTRODUCTION Many myths are linked to the birth of twins. Twin pregnancy has been a fascinating subject and has generated a lot of interest in obstetrics, many religions, communities and cultures. There have always been some naturally, or spontaneously, occurring multiple pregnancies -with twins, most common & the most frequent, then triplets and the much rarer quadruplets. But the frequency has increased enormously since assisted procreation has become available.

5. DEFINITION OF MULTIPLE PREGNANCY DEFINITION: When more than one fetus develops simultaneously in the uterus, it is called multiple pregnancy ( D.C.Dutta ). Many placental species give birth to multiples.

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7. TYPES Monozygotic – multiple (usually two) fetuses produced by the splitting of a single  zygote. Dizygotic – multiple (typically two) fetuses produced by two zygotes. Polyzygotic – multiple fetuses produced by two or more zygotes & may contain all fraternal or combination of identical & fraternal siblings. 7

8. Terminology Two offspring - twins Three offspring - triplets Four offspring - quadruplets Five offspring - quintuplets Six offspring - sextuplets Seven offspring - septuplets Eight offspring - octuplets Nine offspring - nonuplets Ten offspring - decaplets Eleven offspring - undecaplets Twelve offspring - duodecaplets 8

9. Terminology- Cont’d… Thirteen offspring - tridecaplets Fourteen offspring - quadecaplets Fifteen offspring - quindecaplets Sixteen offspring - sexdecuplets Seventeen offspring - sepdecuplets Eighteen offspring - octdecuplets Nineteen offspring - nondecuplets Twenty offspring - icosuplets 9

10. INCIDENCE Global being 1 in 250. Varies from 5.6-46 per 1,000 births Highest rate of twins in Nigeria being 1 in 20 Lowest in far eastern countries( Japan 1 in 200) In India,1 in 80 pregnancies. According to Hellin’s rule, Twins 1 in 80 pregnancies, Triplets 1 in 80 2 , Quadruplets 1 in 80 3 and so on.

11. Etiology of Multiple Pregnancy A woman's chances of having identical –MZ twins are not related to age, race or family history & t he frequency remains constant throughout the globe. Prevalence of dizygotic twins is related to, Advancing age of the mother Increased incidence of twinning is observed with the advancing age of the mother, the maximum b/w 30-35 years & the incidence is markedly reduced thereafter. Influence of parity The incidence is increased specially from 5th gravida .

12. Cont.. Race: The frequency is highest amongst Africans, lowest amongst Mongols and intermediate amongst Caucasians. Hereditary: There is hereditary predisposition likely to be more transmitted through the female (maternal side). Iatrogenic- ART Drugs used for induction of ovulation ( clomiphene citrate or gonadotrophins ) may produce multiple foetuses to the extent of 20-40 %. Revised ART policies have reduced incidence, currently.

13. Iatrogenic Twinning Ovulation induction should be carried out when possible with specific treatments - bromocriptine and pulsatile GnRH to induce single ovulations. With normo gonadotrophic anovulation , the first line of tt for ovulation induction is, clomiphene which is associated with twin rates (10%) and triplet rates to 1%. Tt with FSH causes upto 40 %. Hence, Gonadotrophin tt should be reserved for clomiphene -resistant women & l ow dose regimens should be encouraged. 13

14. TYPES OF TWINS Dizygotic / Binovular / Fraternal Twins Monozygotic/ Uniovular /Identical Twins Zygosity - refers to the genetic makeup of twin pregnancy. Chorionicity - indicates the pregnancy’s membrane status.

15. Genesis & Varieties of Twining Dizygotic / Fraternal / Binovular Twins (80%) Dizygotic twinning is the commonest. Results from the fertilization of two ova either from same or both the ovaries most likely ruptured from two distinct graffian follicles usually of the same or one from each ovary during a single ovarian cycle each fertilized by a separate sperm. All dizygotic twins have two placentae which are dichorionic and diamniotic . 16

16. Binovular Twins - Cont’d… Fraternal twins (like siblings) share about 50 % of their genes, hence can be of different sexes. They look like brothers or sisters born from different pregnancies. Triplets & other higher-order multiples can result from three/more eggs being fertilized, one egg splitting twice (or more), or a combination of both. 17

17. Monozygotic Twins (Identical Twins/ Uniovular - 20%) Arises from a single fertilized oocyte by a single sperm that subsequently divides true or identical twins (or occasionally more). Monozygotic twins (Identical, uniovular ): Twinning occurs at different periods after fertilization and this markedly influence the process of implantation & formation of fetuses & membranes. The fetuses usually share one placenta. Identical twins have the same genes, so they look alike and are of the same sex. 18

18. Timing of division & the results If the division takes place within 72 hours after fertilization (prior to morula 8 cell stage) the resulting embryos will have two separate placentaes , chorions and amnions ( diamniotic-dichorionic or DID). On rare occasions, the following possibilities occur. If the division takes place between the 4th and 8th day after the formation of inner cell mass when chorion has already developed – diamniotic monochorionic twins develop (DIM).

19. Timing of division & the results - Cont’d… If the division occur after 8 day of fertilization, when the amniotic cavity has already formed, a monoamniotic – monochorionic twin develops (MIM). On extremely rare occasions, When splitting occurs after the 13th day of fertilization (during the development of embryonic disc) it results in the formation of conjoined twins called Siamese twins*. * Until the late 1800s conjoined twins were called “monsters.” The term Siamese twins comes from the twin conjoined brothers Chang and Eng Bunker who were born in Siam, now Thailand. When they first arrived in England to become circus exhibits, they were called “The Siamese Twins.”

20. Five type of fusions Thoracopagus (commonest) Omphalopagus (umbilical fusion) Pyopagus (posterior fusion) Craniopagus (cephalic) Ischiopagus (caudal) 22

21. The other possibilities… Superfecundation Superfetation Fetus papyraceous or compressus Fetus acardiacus Hydatidiform mole Vanishing twin Dicordant twins 23

22. Cont’d… Superfecundation : It is the fertilization of two different ova released in the same cycle, by separate acts of coitus within a short period of time. Superfetation : It is the fertilization of two ova released in different menstrual cycles. The nidation and development of one fetus over another fetus is theoretically possible until the decidua space is obliterated - by 12 weeks of pregnancy.

23. Cont’d… FETUS PAPYRACEOUS or COMPRESSUS It is a state which occurs if one of the foetuses dies early. The dead fetus is flattened and compressed between the membranes of the living fetus and the uterine wall. It may occur in both varieties of twins, but is more common in monozygotic twins and its discovered at delivery or earlier by sonar.

24. Cont.. Fetus Acardiacus : It occurs only in monozygotic twins. Part of one fetus remains amorphous and becomes parasitic without a heart. Hydatidiform Mole: A normal fetus and placenta(from the other conceptus ) has been observed by ultrasonography .

25. Cont’d… Vanshing Twins: Serial ultrasound imaging in multiple pregnancy since early gestation has revealed occasional death of one fetus & continuation of pregnancy with the surviving one. The dead fetus (if within 14 weeks) simply ‘vanishes’ by resorption . The rate of disappearance could be to the extent of 40%. Dicordant Twins ( sGR Twins): Birth weight discordance was defined as a difference of 20% or more of the weight of the heavier twin, associated with an intra-uterine growth restriction (10( th ) percentile) of at least one twin. Ultrasound discordance was defined as a difference of estimated fetal weight>20%.

26. DETERMINATION OF ZYGOCITY With the advent of organ transplantation, the identification of the zygosity of the multiple fetuses has assumed much importance. 28

27. Examination of placenta and membranes DIZYGOTIC TWINS: There are two placenta, either completely separated/more commonly fused at the margin (appearing to be one). There is no anastomosis between the two fetal vessels. Each fetus is surrounded by a separate amnion and chorion . And as such, the intervening membranes consist of 4 layers- amnion, chorion , chorion and amnion. In early pregnancy, the decidua capsularis of each sac may be identified under the microscope in b/w chorionic layers. 29

28. Examination of placenta and membranes Monozygotic Twins: The placenta is single. There is varying degree of free anastomosis between the two fetal vessels. AtoA orVtoV anastomosis is ok, but… Each fetus is surrounded by a separate amniotic sac (at times single), chorionic layer be common to both ( diamniotic-monochorionic ) and the intervening membranes consist two layers of amnion only. 30

29. DETERMINATION OF ZYGOCITY Sex: While twins having opposite sex are almost always binovular (also of the same sex) and uniovular twins are always of the same sex. Genetic features : If the fetuses are of the same sex and have the same genetic features (dominant blood group), monozygotic is likely. DNA microprobe technique is most definitive. Follow up study : between 2-4 years, showed almost similar physical and behavioural features suggestive of monozygosity . Skin grafting : Matches fully in MZ, less likely in DZs. 31

30. Conjoined twins Thoracopagus

31. Omphalopagus

32. Pyopagus

33. Craniopagus

34. Ischiopagus

35. MULTIPLE GESTATION PROCESS If the division takes place within 72 hours after fertilization (prior to morula stage) resulting embryos have two separate placenta, chorions & amnions - diamniotic-dichorionic or D/D (30%). If the division takes place b/w 4th to 8th day after formation of inner cell mass when chorion has already developed- monochorionic , diamniotic twins develop D/M (66%). 37

36. 38 History symptoms General examination Abdominal examination Internal examination Sonography Radiography Biochemical tests Diagnosis of Multiple Pregnancy

37. 39 History History of ovulation inducing drugs, for infertility - ART. Family history of twining  

38. SYMPTOMS Some of the symptoms are related to the undue & u nusual rate of enlargement of the uterus: Increase nausea and vomiting in early months. Cardio-respiratory embarrassment in the later months—such as palpitations, shortness of breath. Greater tendency of swelling of the legs, varicose veins & haemorrhoids Excessive fetal movements(& FHR) noticed by an experienced parous mother.

39. General examination Prevalence of anaemia is more than in singleton pregnancy. Unusual weight gain, not explained by preeclampsia or obesity, is an important feature. Evidence of preeclampsia 25% is a common association. 41

40. 42 Abdominal examination Inspection The elongated shape of a normal pregnant uterus is changed to a more “barrel shape’ and the abdomen is unduly enlarged. Palpation Increased height & girth of abdomen: The height of the uterus is more than the period of amenorrhoea . This discrepancy is evident from mid pregnancy. Palpation of too many fetal parts Finding of two fetal heads or fetal poles makes diagnosis certain.

41. Internal examination: In some cases, one head is felt deep in the pelvis, while the other one is located by abdominal examination. Presentation and lie of the fetuses sd be checked . Vertex & vertex - 50% 1 st breech 2 nd Vertex- 30% 1 st Vertex 2 nd breech- 10 % Both breech - 10% 1 st Vertex 2 nd transverse & so on…..

42. Auscultation Simultaneous hearing of two distinct fetal heart sounds located at separate spots with silent area in between gives a certain clue in the diagnosis of twins, provided the difference in heart rates is at least 10 beats per minutes . More than one heartbeat heard by a provider using a hand-held ultrasound device (Doppler). 44

43. INVESTIGATIONS Sonography , 3D USG, Doppler velocimetry , MRI Radiography Biochemical tests 45

44. Sonography Sonography Confirmation of diagnosis as early as 10th weeks of pregnancy Viability of foetuses, vanishing twin in the second trimester. Chorionicity of the placenta. Pregnancy dating, Fetal anomalies Fetal growth monitoring at every 3-4 weeks interval. Presentation and lie of the fetuses. Amniotic fluid volume. Twin peak sign/ Lamda sign Fetal surveillance is maintained by serial sonography , every 3-4 weeks interval. 46

45. Radiography Two fetal heads and spine- Presentation and lie of the fetuses could be seen. Triplets or conjoined twins could be diagnosed accidentally.

46. Biochemical tests Abnormal results on prenatal screening tests  around 16 weeks of pregnancy for certain birth defects. Maternal serum Human chorionic gonadotrophin , Maternal serum alpha feto protein, Unconjugated oestriol 48

47. DIFFERENTIAL DIAGNOSIS Hydramnios Big baby Fibroid or ovarian tumour with pregnancy Ascitis with pregnancy 49

48. MANAGEMENT Antenatal management Early diagnosis Counseling Management during labour Management during puerperium Management of Complications 50

49. Prenatal screening GUIDELINES FOR COUPLES & CARERS To couples considering treatment for infertility. Give detailed information on the chances of a multiple pregnancy, on the consequent risks and implications for the children and the family and about fetal reduction. 51

50. Prenatal screening Prenatal screening: Ensure that parents understand the options available if an anomaly is present in only one fetus, (selective feticide). Provide special prenatal classes, in collaboration with local parents of twins group, for parents and grandparents, including guidance on feeding, equipment, sources of information and practical help, promotion of individuality and language, and the needs of older siblings. 52

51. Management Antenatal management Advice Diet : Increased dietary supplement is needed for increased energy supply to the extent of 300 K cal per day. Increased rest at home & early cessation of work to prevent preterm labour. Even if a woman with multiples has no signs of preterm labor, it is recommended that she cut her activities from 20th to 24th weeks, even sooner and to rest several times a day if she is expecting more than two babies. Supplementary therapy : i ) Iron therapy to be increased to the extent of 60-100 mg per day. ii) additional vitamins, calcium and folic acid (1 mg) are to be given.

52. Antenatal management Interval of antenatal visits Women with multiples need to visit their health care providers more frequently. These extra visits can help prevent, detect and treat the complications that develop more often in a multiple pregnancy. Health care providers may recommend twice-monthly visits during the second trimester and weekly or more visits during third trimester . Hospitalisation : Hospital admission only for bed rest is not essential. Improves utero -placental circulation.

53. Assessment of fetal growth Starting around the 20th week of pregnancy, a health care provider monitors for signs of preterm labor. The provider may do an internal exam or recommend a vaginal ultrasound to see if the woman's cervix is shortening (a possible sign that labor). The biophysical profile, which combines the non-stress test with an ultrasound, is done. As a multiple gestation progresses, regular check on blood pressure, & regular ultrasounds starting around 20 weeks of pregnancy ,, etc, to check that all babies are growing at about the same rate. 55

54. DURING PREGNANCY Provide written information including contacts of local & national organizations, for families with multiple births. In monochorionic pregnancies, ensure that parents understand the implications and need for close monitoring. 56

55. INDICATIONS FOR CAESAREAN SECTION Obstetric causes: Placenta praevia Severe preeclampsia Previous caesarean section Cord prolapse of the first baby Abnormal uterine contractions Contracted pelvis Fetal causes: Both fetuses or the first in non cephalic presentation, Complication of IUGR, Conjoined twins Monoamniotic twins Monochorionic twins Collision of both the heads at brim preventing engagement of either. 57

56. MANAGEMENT DURING LABOUR Skilled obstetrician should be available Presence of ultrasound in labour ward The patient should be in bed Use of analgesic drugs Careful fetal monitoring Internal examination should be done An intravenous line with RL solution 58

57. Birth & the Neonatal period Ensure that each umbilical cord and infant is labelled immediately. All placentae should be examined by an experienced midwife or obstetrician for chorionicity , sites of cord implantation and vascular anastomosis . Determine zygosity by sex, chorionicity or (in like-sex dichorionic twins) DNA analysis (of blood or placenta) or blood - genetic markers. Ensure that babies' clothes are readily identifiable so that parents (and staff) can recognize babies from distance. 59

58. Birth and the Neonatal period Ensure that staff label and refer to the babies by their names. Consider co-bedding the twins. Take photographs of the babies together (particularly if one is likely to die). Offer practical help to the mother throughout all feedings. Whenever practicable, nurse babies in the same ward & discharge from hospital at the same time. Ensure that the neonatal unit has a special protocol if a multiple birth baby dies, as well as literature to give and contact with a bereaved parent of twins who can offer immediate support. 60

59. THE PRE-SCHOOL YEARS Encourage parents, To promote the individuality of their children (and encourage grandparents and friends to do the same) by, avoiding similar names, making them readily distinguishable giving them times apart from an early age; promote language development by providing one-to-one communication from infancy. 61

60. PROGNOSIS Maternal morbidity is increased in twins than in a singleton pregnancy due to the prevalence of complications and increased operative interference. There is a higher perinatal mortalityesp . In MZTs, due to sharing of a single gestational sac. Death is mostly due to haemorrhage , PIH and anemia. Because of increased risk to both mother and baby, compared to that of a singleton pregnancy, twin pregnancy is considered high risk and as such should be delivered in a hospital. 62

61. Complications Women who are expecting more than one baby are at increased risk, t he more the babies, the greater her risk for complications . There is an exaggerated adaptation of all body systems of the mother specially of the cardiovascular system. Cardiac output is higher & Plasma volume during pregnancy is much greater with lower Plasma proteins. 63

62. Complications MATERNAL – DURING PREGNANCY Increased severity of nausea and vomiting Urinary infection is more common Gestational hypertension & Pre- eclampsia ( low Plasma proteins) Gestational diabetes Haematocrit and haemoglobin is lower than in singleton pregnancy causing anaemia . Hydramnios Antepartum haemorrhage -Placenta previa , Abruption Malpresentation Preterm labour Mechanical distress

63. Complications DURING LABOUR Early rupture of membranes Cord prolapse Prolonged, difficult labour Increased operative interference Intrapartum haemorrhage

64. Complications During puerperium Postpartum haemorrhage Sub involution Infection Lactation failure Thrombo embolism

65. Complications FETAL Abortion Prematurity Congenital anomalies Malpresentation Asphyxia and still birth Intra uterine growth restriction Intra uterine death 67

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67. Preeclampsia (25%) Women expecting twins are more than twice as likely as women with a singleton pregnancy to develop this complication. Severe cases can be dangerous for mother and baby, the babies may have to be delivered early to prevent serious complications. 69

68. Pregnancy Related Diabetes Women carrying multiples are at 2 to 3 fold, increased risk of this pregnancy related diabetes. This causes the baby to grow large, increasing risk of injuries to mother and baby during vaginal birth. Babies born to GDM women also have breathing & other problems during the newborn period. Early diagnosis and management of the complications protect mother and babies. 70

69. Common complications Prematurity About 80 percent of twins, more than 90 percent of triplets, and virtually all quadruplets and higher-order multiples are premature. The length of pregnancy decreases with each additional baby. On an average, most singleton pregnancies last 39 weeks; for twins, 35 weeks; for triplets, 32 weeks; for quadruplets, 29 weeks. 71

70. Common complications Low Birth Weight (LBW) More than half of twins and almost all higher-order multiples are born with LBW (less than 2,500 grams) . LBW can result from premature birth and/or poor fetal growth. Both are common in multiple pregnancies. 72

71. Common complications-LBW LBW babies, especially those born before 32 weeks and/or weighing less than 500 grams, are at increased risk of health problems in the newborn period, as well as disabilities - intellectual disabilities, cerebral palsy , vision and hearing loss . While advances in caring for very small infants has brightened the outlook for these tiny babies, chances remain slim, that all infants in a set of sextuplets will survive. 73

72. TAPS Doppler shows blood flow differences in mid cerebral artery, Difference of Hb as 11gm for donar twin vs 20gm for reciepient twin. This occurs due to smaller anastamosis . 74

73. TRAP TRAP - Twin Reversed Arterial Perfusion 75

74. 76 sGR Babies

75. Common complications TWIN-TWIN TRANSFUSION SYNDROME (TTTS) About 10 percent of identical twins –MCDA who share a placenta develop this complication. Here, a connection between the two babies' blood vessels in the placenta causes one baby to get too much blood & the other too little. Severe cases often resulted in loss of both babies. 77

76. In Poli-oli syndrome, the donar twin has, Anemia, Oliguria , Oligohydramnios , Hypotension the reciepient twin has,…… 78

77. Quintero staging in TTTS In Poli-oli syndrome, hydramnios , visible bladder, abn . doppler in umbilical artery, hydrops & fetal demise are measured. 79

78. Comparison of laser surgery& amniocentesis . TTTS now can be treated with laser surgery to seal off the connection between the babies' blood vessels. It also can be treated with serial (repeated) amniocentesis  to drain off excess fluid. Removing the excess fluid appears to improve blood flow in the placenta and reduces the risk of preterm labor. Both procedures improve the outlook for babies. A septotomy improves the outlook for babies 80

79. Laser Surgery versus Amniocentesis However, recent studies suggest that laser surgery may save more babies and cause fewer neurological problems (such as cerebral palsy) in survivors than amniocentesis. For example, an European study found a 76 % survival rate for at least one fetus after laser surgery compared to 56 % for serial amniocentesis. Another advantage of laser surgery is that only one treatment is needed, while amniocentesis generally must be repeated more than once. 81

80. SELECTIVE FETOCIDE Embryo reduction Embryo reduction techniques were developed initially to carry out selective fetocides in cases of fetuses affected by some malformation or genetic disorder. Later the technique was applied to the reduction of one or more fetuses in cases of high-order multiple pregnancies. 82

81. Multi Fetal Pregnancy Reduction (MFPR) The procedure is variably named: selective abortion, selective reduction, but the preferred term is Multi Fetal Pregnancy Reduction (MFPR). It is now recognized as a safe and effective method to improve outcome in multiple pregnancies, esp. in quadruplets and higher order pregnancies, arguably in triplets. The procedure is performed under ultrasonic control at 11 or 12 weeks gestation by injecting into the chest of each fetus 1–2 ml of KCl , 2 N. 83

82. MFPR The embryos selected for reduction are those which are in the upper part of the uterus, those which have increased nuchal translucency or other ultrasonographic markers of risk. Some authors advocate karyotyping by chorionic villous sampling prior to MFPR, but this requires an additional procedure and, when karyotype results are available, it is not always easy to be certain which embryo has the given karyotype. 84

83. MFPR In addition, if two viable embryos are left, the risk of chromosomal abnormality per pregnancy is only twice that of the age of the woman and subsequent amniocentesis could be performed at a later stage, if the woman wishes to do so. 85

84. 86 IUD Dead fetus syndrome, causing DIC Appearing twin Vanishing twin-21% Conjoined twins

85. 87 Fetal anomalies* …… The most common types of congenital anomalies were as per journal findings, Cardiovascular anomalies (51, 28.0%), Anomalies of the central nervous system (24, 13.2%), Genito -urinary system (25, 13.7%), Chromosomal anomalies (21, 11.5%), Musculoskeletal (19, 10.4%) and Others ( 31, 17.0%) including facial clefting , oesophageal atresia , other anomalies of the digestive system, syndromes (2.7%) and multiple anomalies (2.2 %) Congenital anomalies in twins: a register-based study, S.V. Glinianaia , J. Rankin, C. Wright. Human Reproduction , Volume 23, Issue 6, June 2008

86. 88 Conclusion