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Saturday, 1 October 2016

(selingan) : Zwillinge = Twins

In the name of Allah, Most Compassionate, Most Merciful.

Solving an infertility case is like solving a puzzle - be it crossword puzzle or Sudoku or Kakuro or jigsaw puzzle. Each piece has a unique cut which fits into its proper place. You have to be meticulous in searching for the place for each piece. Sometimes : you are just lucky when you put that piece randomly (because you are left with no more clue), or when you try every piece of the same colour/appearance/shape into that slot ..... and you can solve it faster if you work as a team with others who have similar interest in solving the puzzle. 

No 2 pieces have exactly the same cut  no 2 patients have exactly the same clinical profile / problem(s), however similar/identical they often appear.


Twins (and multiple pregnancies) never cease to fascinate many of us.
Especially identical twins.

One doctor was so 'intrigued' by twins until he ran experiments on them, mostly children, resulting in their deaths. Remember what the infamous Josef Mengele did at the Nazi concentration camp in Auschwitz, Poland about 70 years ago? (I don't want to insert his 'doctor' title as he did not uphold the 'primum non nocere'  aka 'first do no harm' oath). These children's lives were spared from being sent straight into the gas chambers, but only temporarily, as they became guinea pigs and were then subjected to multiple 'so called medical experiments' before they were killed at the same time with their 'untested/controlled twin' and their bodies were then dissected. Sometimes they died before the experiments were concluded, because of complications .... 

The unspeakable abuses by one human being (there were actually other doctors in Auschwitz) onto others.
Imagine how these twin children suffered...
Imagine if they were your own children...
For example, 
imagine their eyeballs being injected with dye in an attempt to change the colour...
Or imagine them being sewn back to back in an attempt to create conjoined twins...
Only a few lived to tell the stories....

Forget about Mengele.


Twin Pregnancy

(for the medical students, with disclaimer : this serves as a guidance only, I have never been a lecturer and I am also not your teacher. You are welcome to correct me, thank you in advance) 

Incidence of multiple pregnancy (remember Hellin's rule) : 
- twins 1:80
- triplets 1:80 x 80
- quadruplets 1: 80 x 80 x 80

Know about possible causes of uterus larger than date:
1. Wrong date
2. Multiple pregnancy
3. Polyhydramnios
4. Fetal macrosomia
5. Uterine fibroid
6. Ovarian mass
7. GTD (especially in 1st trimester) as it is unlikely that a GTD continues beyond the 1st trimester without surgical intervention. 

Then, know about the 'abdominal findings' of a multiple pregnancy :
- uterus larger than date (excessive fundal height by .... cm)
- signs of 'excessive uterine size' : tense-looking abdomen, shiny, marked striae gravidarum
- multiple fetal poles (at least 3)
- multiple FHR in separate quadrants

Know what to ask her, about :
- history of fertility treatment
- family history of (dizygotic) twins
- symptoms related to twins : excessive symptoms of hyperemesis gravidarum, symptoms of 'tense abdomen',  frequent or significant fetal movements
- in mothers who have children, ask about the welfare of her children at home whilst she's admitted (show that you care) 
- additional info already told told to her by her obstetrician : twins status, type of twins, plan of delivery, latest Hb.
- symptoms related to complications eg symptoms of APH, preterm contractions , admission, therapy etc

... when talking about complications;
We, doctors other than Mengele, are more concerned with below mentioned two factors as they have associated possible complications :

1. general risks
2. risks related to its chorionicity and amnionicity

1. Their chorionicity : sharing a single placenta (monochorionic) vs not sharing (dichorionic) 
2. Their amnionicity : sharing a single amniotic sac (monoamniotic) vs not sharing (diamniotic)

mono = one
di = two

Our concern gets bigger if the twin pregnancy is monochorionic (sharing one placenta) and the worst when it is also monoamniotic (sharing a single amniotic sac). 

As in other aspects, be systematic when discussing about complications of twins. First, temporarily put aside chorionicity and amnionicity. Having twin pregnancy is already considered 'high risk'. So, know at your fingertips : the general risks of twin or multipe pregnancy, regardless of its zygocity, chorionicity and amnionicity. Again, be systematic , divide the risks/complications into : the risks to the mother and to the fetuses and these can be further divided into antenatal, intra-partum and postnatal risks/complications. 

Maternal risks/complications:
- Antenatal : excessive symptoms of hyperemesis gravidarum which may require  frequent hospital admissions, pressure symptoms, polyhydramnios, PPROM, preterm contractions, pre-eclampsis 3-fold x, eclampsia 6-fold x, anemia, APH (placenta previa, abruptio placenta), Caesarean cestion. 
- Intra-partum : Spontaneous ROM, cord prolapse, abruptio placenta, interlocking of twins, emergency Caesarean section
- Postpartum : uterine atony, PPH, retained placenta, endometritis

Fetal risks :
Antenatal : fetal anomalies (structural and chromosomal), miscarriage / death of one twin / vanishing twin, IUGR
Intrapartum : malpresentations, interlocking of twins
Post partum : complications of prematurity, increased perinatal morbidity and mortality

Then, discuss on the risks of having monochorionic twins and monoamniotic twins and your list of possible complications gets longer.

In monochorionic twin pregnancy, be it diamniotic or monoamniotic, in addition to general risks of twin pregnancy are the consequential risks of 'sharing one placenta'  (remember the functions of placenta, imagine the placenta as their food supplier or kitchen pantry and now the twins have to share the 'food' between them) :

1. Inter-placental vascular anastomoses : A-A, A-V, V-V : causing miscarriage, amniotic fluid discordance, fetal growth discordance, unequal placental sharing, selective IUGR (they may not get TTTS yet) and eventually TTTS.

2. Twin-to-twin transfusion syndrome (TTTS) : a-v anastomosis with net flow in 1 direction (recipient : hypervolemia, polyhydramnios, hypertension, cardiomegaly, CCF, hydrops foetalis, death) and donor : hypovolemia, anemia,  severe oligohydramnios, severe IUGR, hypotension, poor renal perfusion, anuria, , stuck twin.
3. Fetal anomalies (usually due to A-A malformation)
4. Acardiac twin with Twin-Reversed Arterial Perfusion (TRAP) sequence 
5. Risks to the surviving twin, after death of one twin : 25% risk of co-twin death, 25% risk of neurological damage.

In monoamniotic twin pregnancy (which is always monochorionic too), in addition to the general risks of twin/multiple pregnancy and the risks of monochorionic pregnancy, you have to add consequential risks of 'sharing one room/ amniotic sac' too :

1. Cord entanglement

2. Cord compression
3. Locked twins
4. Other fetal anomalies 

Don't forget about conjoined twins
Conjoined twins (types : craniopagus, thoracopagus, omphalopagus, ischiopagus, pygopagus)
Monochorionic twin pregnancy is an example that :


be it monochorionic-diamniotic or (monochorionic) monoamniotic.

That is why, we doctors, must find out about its chorionicity and amnionicity.
Not so much about its zygocity (identical monozygotic vs dizygotic).
Not so much about their sexes; unless they are of different sexes, then you know that they are dizygotic twins, therefore dichorionic (diamniotic).

Know how to determine its chorionicity (and amnionicity). Before that, know about : how the timing of monozygotic twinning/splitting affects their chorionicity and amnionicity.

As in one of our undergraduate textbooks, I used to remember the types of monozygotic twins (dizygotic twins are always dichorionic) according to the day-age of the embryo when it splits into 2 :

Days 1-4 : dichorionic (diamniotic)
Days 5-8 : monochorionic diamniotic
Days 9-12 : (monochorionic) monoamniotic
Days 13 or older : conjoined twins

But upon knowing what is happening inside the developing embryo at each stage, I have understood better. See below and you'll get excited as I still am (and you'll want to know more). Open up your Embryology textbook.

- Cleavage stage (just cell division, no cell differentiation yet) : from 1-cell embryo, then 2-cell, 4-cell and further dividing until morula stage : always dichorionic (diamniotic)

- Early blastocyst stage (day-5-7) : the embryo begins its cell differentiation into the 'inner cell mass' (ICM) and the 'outer cell mass' or the trophectoderm (TE) and there is also a fluid-filled cavity called blastocoel. We know that the ICM is located inside while the TE cells surround the peripheral of the blastocyst. We also know that the ICM will eventually form the fetus and the amnion, while the TE will form the fetal placenta (chorionic frondosum) and its chorionic membrane. So, splitting of the ICM (which is inside the blastocyst) will form monochorionic twins as the TE does not usually split together.

- Late blastocyst stage (day-8-12) : now there is further cell differentiation. Remember? The ICM will eventually form the fetus and the amnion later on. During this phase, the ICM further differentiates into the embryonic disc which is now bilaminar (2-layers) : the epiblast and the hypoblast. (At this late stage, the blastocyst has hatched from its zona pellucida ZP and implantation begins). This bilaminar embryonic disc lies in between the ballooning amniotic cavity (above the epiblast) and the yolk sac (below the hypoblast). Since the amniotic cavity is already present at the time this bilaminar embryonic disc splits into twins, these fetuses generally share the same amniotic cavity (membrane), thus creating (monochorionic) monoamniotic twins. They also share the same yolk sac too (not all the time, but always, monoamniotic pregnancy usually has one yolk sac, diamnitic pregnancy usually has 2 yolk sacs). 

-  to infinity and beyond!   day 13 or beyond : During gastrulation process in the 3rd week after fertilization; the primitive streak is formed, the bilaminar embryonic disc further differentiates into 3 primary germ layers : the endoderm (from the hypoblast), the mesoderm and the ectoderm (both from the epiblast). Splitting of the primitive streak is often incomplete, resulting in conjoined twins : the types depending on the site they are still attached to each other. 

Note :

- We Obstetricians always mention dichorionic twins, not dichorionic diamniotic twins because dichorionic twins are always diamniotic. The term diamniotic is redundant in this case.
- We also mention monoamniotic twins, not monochorionic monoamniotic, because monoamniotic twins are always monochorionic. The term monochorionc is redundant in this case.


Hope that now, you understand better.
The incidence of multiple pregnancy is higher due to increased number of assisted reproductive therapy cycles using ovarian stimulation drugs. You'll come across them in your ObsGyn posting. So, read because you want to know more, so that you can manage/treat them well. You'll soon be our colleagues. 

By the way, do you still remember that (unless you slept during SPM Biology class, dear): our mitochondrial DNA (not nuclear DNA) in our cells originated from our biological mother's oocyte's mitochondrial DNA? Yes. Maternal oocyte's mitochondrial DNA. No paternal input. So, we actually share about the same mitochondrial DNA composition because they all originated from our great, great, great (many times great) grandmother's ovum's mitochondria : Eve's ovum's mitochondria. Wow! .......

I had forgotten what I learned in medical school about mitochondria except for its shape : it is bean shaped.

End of academic discussion.


(All praise is due to Allah)

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