What is the cause of my Failed IVFs?

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Question: My husband and I had gone through 3 IVFs without success, does it mean that our chance of pregnancy is very slim? Is it due to my body condition?

 

Dr Helena’s Answer: To achieve a successful pregnancy through IVF, there are some basic pre-requisite factors:

 

(1) The age of the couple, especially the female partner
(2) The duration of Subfertility
(3) good quality and quantity of eggs and sperms to make good quality embryos
(4) a conducive uterus environment for implantation

Studies had also shown that there is a increasing cumulative pregnancy rate for women who went through a few cycles of IVF.

However, after going through three IVF without success, one may wonder whether there is light at the end of the tunnel.

Being a fertility doctor, I can understand how frustrating it would be. However, these IVF cycles which did not work out, may contain valuable information about your fertility. As we know, apart from being a treatment in its own right, IVF also serve as a diagnostic tool in its own right, by telling us how you respond to the medications, how your eggs and sperms qualities are, and how your embryos qualities are.

There a a few aspects we may consider to improve on for your next IVF treatment:

The IVF treatment protocol
The clinic
The sperm
The eggs
The uterus

Here are some consideration for you:

(1) The IVF Treatment protocol.

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While the IVF treatment protocol is pretty standard, every patient responds differently to the types and dosage of IVF medication. Each cycle teaches us how your body responds to the injections to help your follicles grow. It takes a good IVF doctor to be able to decide on the right dose and right type of medications, to get you to produce an optimal number of high quality eggs. Some young patients with normal ovarian reserve grow well in response to a standard protocol, patients with poor ovarian reserve and those with PCOS need a lot of extra attention and closer monitoring.

 

However, at the end of the day, some of this is trial and error. A good previous record can help us to learn from each cycle , until we can customize the perfect protocol for you
(2) The IVF clinic/centre.

 

It is important to note most IVF clinic/ centre are pretty standard, there are variations in terms of their operations and quality controls, and hence their success rates. In Malaysia, there is still no regulatory body that mandates each IVF clinic/ centre to report their success rates. However, it is important to look for credible centres with proper accreditation to ensure the quality of your IVF treatment.

 
(3) The sperm.

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Poor sperm quantity & quality may be associated with failed fertilization of an egg during an IVF but with the advent of ICSI, these problems are easily over-come. However, if the sperms are have high DNA fragmentation, the resulting embryos may still have poor quality. Simple lifestyle changes such as stop smoking & alcohol, weight loose, exercise and consumption of good quality food which are rich in anti-oxidants are some of the key elements in improving sperm quality and IVF outcome

(4) The eggs.

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Human egg is a thousand times bigger than the sperm, and that the energy for cell division during embryo cleavage comes from the mitochondria in the egg’s cytoplasm, therefore, egg quality is another important factor for IVF success. Poor egg quality leads to poor embryos and hence failed IVF. The problem is that it’s very hard to make this diagnosis, as there is no blood tests or medical technology to identify poor eggs prior to an IVF cycle. In fact, IVF is a diagnostic tool in it own right, as egg quality can be assess during an IVF. To improve egg quality involves making lifestyle changes, improving diets, and sometimes some alternative medications such as DHEA.
(5) The uterus.

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It is probably a very Oriental or ‘Chinese’ believe that failure to get pregnant/ implantation is always the fault of the uterus. It is not unusually to hear the terminology of ‘cold uterus’ being cited for the reason for not getting pregnant. Hence, the idea of surrogacy has become very popular recently because of the disproportionate amount of media attention it attracts, and especially so when cross borders IVF had become extremely popular with the ease of medical access overseas. This had lead to the idea that the best medical solution for them after many failed IVF cycles is surrogacy. After all, the fact that the embryos are not implanting means the uterus must be ” defective” , so doesn’t it make sense to use a fertile woman’s uterus as an incubator for 9 months ? However, the truth is that surrogacy is an expensive and complex treatment option, which is best reserved for women without a uterus. It is also important to stress that Surrogacy is ILLEGAL in Malaysia. Research shows that the reason for failed implantation is much more likely to be genetically abnormal embryos ( because of poor quality sperms or eggs), rather than a uterine problem. However, in about 20-30% of women, failure in implantation maybe due to some small correctable issues in the uterus such as polyps or fibroids. These issues can be dealt with easily without having to resort to surrogacy

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Does IVF has 100% of pregnancy rate ?

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Question: My husband & I had tried conceiving through IVF but did not succeed. If we try IVF again, would my chances of getting pregnant lower than others? How do I increase my chance of success?
Dr Helena’s answer: The advent of IVF had greatly revolutionize the world of reproductive medicine. Millions of babies had been born, as the result of IVF. Without IVF, the birth of these babies would not had been possible due to various infertility issues
 
However, is IVF a magic bullet with 100% of pregnancy success rates? 
 
The answer is no, as we know, IVF’s success rate is not 100%.  
 
A few important factors associated with success rates of IVF is women’s age, the duration of Subfertility and whether there is any previous history of pregnancies. Some other factors includes the quality and quantity of eggs, sperm quality & lifestyle and habits 
 
For couples who didn’t succeed in getting pregnant during their first round of IVF, it is logically to wonder, whether they will ever get pregnant in their subsequent cycles of IVF
Generally the overall success rates of ONE IVF for a woman who is under the age of 35 is around 60-70%. We also know for a fact that a frozen embryo transfer has a higher pregnancy rate compares to a fresh embryo transfer.  For most women under 35, there is a good chance that she produces more than 2 good quality embryos each IVF cycle. most of the time, these excessive embryos can be frozen and can be used in the future. Technically speaking, ONE IVF cycle can potentially resulting more than one pregnancy, if the woman has lots of embryos and keep coming back to get them transfer into her uterus.
 
Coming back to the question, we know for sure that if you have a good number of embryos from the result of ONE IVF, the chance of you getting pregnant with the subsequent Frozen embryo transfer is extremely likely, especially if you are under the age of 35

However, if you have no embryos frozen, what is your option?

This chart below showed a cumulative live IVF births from a study conducted.

 

Cumulative Birth Rates

This study looked at all the women under the age of 42, who are going through IVF.

The study revealed that the pregnancy rate is around 40% in this group of women after they completed their first cycle of IVF. For those women who did not get pregnant the first round and went on having the second round of IVF, there were another 20% who got pregnant after the second round. Therefore, by the 4th IVF cycle, around 80% of women would have achieved a live birth.

 

This statistic clearly shows that if you  persevere and keep moving on, chances of you getting pregnant by the end of the 4th IVF is around 80%.

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Therefore, it is not unusual for Fertility doctors to encourage our patients to keep moving on because the statistics had clearly show us the evidence.

To improve your chance of pregnancy for the next IVF, it is important to improve the quality of your eggs and sperms by eating healthy and  improve lifestyle, quit habits which can potentially jeopardize your success rates such as smoking, alcohol and stress. Speak to your fertility doctor about what are the other options in your IVF treatment.

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Is IVF Painful?

 

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Question: I am a person who is fearful of pain. I gathered that going through IVF will required multiple injections, surgery and other procedures which are painful. Is it true?

Dr Helena’s answer:

IVF sounds daunting to many people. A lot of us have perceptions that it is extremely expensive. Some of us thinks that it would bring us a lot of inconvenience, such as having to go to hospital everyday, lay in bed for a few months, quit our job and etc

One of the greatest fear many had was the perception of pain associated with IVF procedures. The thought of having daily injections made most of us wanting to run away and hide from the doctors. Some people are scared thinking about the egg retrieval procedures. Some are dreading the embryo transfer procedure, thinking that it would bring great pain and discomfort. Some dread the injections which are taken after the procedure, which are the progestogen injections, aimed to support the lining of the uterus whilst the embryos are implanting.

However, with the new development and breakthroughs in the world of reproductive medicine, IVF procedures had become more and more comfortable and easy to management, with minimal disruption to daily life.

First and foremost, the durations of injections had been shortened significantly with the use of antagonist injections in IVF. This method of doing IVF is called the antagonist cycle or the short protocol. So, instead of having 3 weeks of injections in the agonist cycle or long protocol, the advent of antagonist injections had lead to a shortened period of 10-12 days of injections. This had greatly reduce the discomfort one needs to go through with injections.
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The use of self-administered FSH injection pens with extremely fine needles, had significantly cut down the pain one experienced during injections. This self- administered injections pens are given to patients to take home, and the injections are administered by patients themselves, so patients do not need to come to the clinic or hospital to have their daily injections. The needles used are similar to the ones used in the insulin injection pens, which is extremely fine and almost painless.

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There is also another long acting FSH injection which given at the beginning of an IVF cycle and can last for 7 days. After the initial injection, the patient need not take FSH injection for the next 7 days, which significantly cuts down the number of injections required.

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The egg retrieval procedure which usually happened after 10-12 days of injections involved having a light sedation in an operating theatre. In the past, the use of certain sedations such as Valium, Dormicum or pethidine administered by the IVF doctors whilst performing the egg retrieval procedure had appeared to be increasingly unsafe. In many IVF units, a proper IVF operating theatre with a trained Anaesthetist giving sedation during the egg retrieval procedure is becoming a norm and deemed acceptable in terms of safety. One of the advantage of the involvement of an Anaesthetist is that egg retrieval procedure is becoming almost painless, and hence optimizing patient experience in IVF.

 

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Embryo transfer procedure is usually carried out 3-5 days after the egg retrieval. During the procedure, the embryos which were created following fertilization of the retrieved eggs with sperms are replaced into the uterus. This procedure is performed without anaesthesia or sedation, is relatively pain free. The experience is almost the same as having a cervical smear. Therefore, women should not feel fearful about having an embryo transfer.

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After the embryo transfer, to support the uterus lining and to ease implantation, a
Progestogen is prescribed. In the past, progestogen is administered by injections. These injections are usually painful and cause local irritations, which is uncomfortable and unacceptable to many. With the advent of effective oral and vaginal suppository preparations, studies had shown that these forms of progestogen are equally effective in delivering progestogen to uterus, injectable progestogen had slowly becoming a thing of the past in many IVF centres. This has also greatly cut down the pain experience in IVF

In conclusion, with rapid modernization in reproductive medicine & technology, IVF had become relatively painless. It is importantly to find out more information on IVF before you embark on this journey.

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Is IVF Expensive?

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Question: My Husband & I had been married for 8 years, we have tried many different methods of getting pregnancy with no avail (except IVF). The reason I have not attempted IVF is because I heard that it is extremely expensive with low success rates, is this true?

 

Dr Helena’s Answer: Many people have a lot of myths and misunderstanding about IVF. In fact, IVF started in the 1970’s with many controversies. It used to be regarded as cultic practice in science, intertwined with many religious, social and ethical controversies

However, many years had gone by and IVF had progressed in leaps and bounds in its technology and approach, proving to the world its value and safety. At the turn of this century, reproductive doctors and scientists had achieved many new innovations and breakthroughs, to make IVF more accessible and safer. Hence, IVF had gradually become the mainstream in reproductive science, making the dreams of having children a reality for many couples

However, it is not unusual to find that people are still weary about IVF, and there are still myths and misconceptions surrounding IVF.

One of the myths about IVF is that it’s extremely costly. We hear stories that people had to ‘loose an arm or a leg’ to be able to afford IVF.

The truth is that IVF cost had reduced remarkably for the last 10-20 years, thanks to many creative innovations, especially in the advent of cost effective medications, culture mediums and lab equipments. The advent of a new freezing technique, called vitrification, allows IVF scientists to freeze embryos more effectively to allow storage of excessive embryos, to be used later, cutting down the need to repeat another IVF cycle, making IVF more cost effective.

The cost of IVF in Malaysia is generally ranging between RM12,000-RM20,000. The price range varies because of differences in clinical and laboratory settings, medications used and etc

The success rates are generally good depending on the age of the women. For women aged below 35, the success rate is about 60-80%. For women above the age of 35 but below the age of 40, the success rate is around 50%. The success rate fell dramatically after the women crossed 40 years of age.

There is recent study on Danish population about the cost effectiveness of IVF. The study followed almost 20,000 Danish women undergoing fertility treatments including IVF. Within three years, 65% of the women had given birth, with the figure rising to 71% within five years.

Therefore, it is important to find out more about IVF before deciding on or against it.

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Can IVF Cause Cancer?

 

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Can IVF Cause Cancer?

 

Today’s post addresses a question that I am often asked at the clinic – Can IVF cause cancer?

This concern very likely stems from a study done 12 years ago, which has since been well-publicised. It reported that the use of Clomid, which is a fertility medication widely used to treat ovulatory dysfunction in women, might increase the risk of breast and uterine cancer.

 

Understandably, this has caused some infertility patients to wonder if the treatments they will undergo are safe. Therefore, today I’d like to reassure you by providing references to other studies on the subject.

It’s important to note that since that study was first published, more studies have been conducted and most have found no significant link between Clomid use and cancer risk. One such study, which in fact offers the strongest evidence that Clomid and other ovarian-stimulating drugs do not increase the risk of ovarian cancer, comes from the Cochrane Review.

Published in 2013, the review looked at studies from 1990 to February 2013 that involved 182,972 women. The review not only found no evidence of increased ovarian cancer in women who use any fertility drug, but also pointed out that studies claiming there is an increased cancer risk were unreliable. This is because their sample sizes were too small for drawing conclusions and they did not take into consideration other potential risks for cancer.

For example, if a woman has never experienced pregnancy, her risk of cancer increases. Certain causes of infertility can also cause an increased risk of cancer, for example obesity, PCOS and endometriosis. So in fact, the increased risk of cancer noted in those studies may not be related to the medications at all.

In fact, ironically, some studies showed a decreased risk of developing breast and uterine cancer among infertile women on Clomid, in comparison to infertile women who did not seek treatment for infertility.

There are two other studies, with substantial sample sizes, which included 25,108 women from the Netherlands who received IVF treatment between 1980 and 1995, found that there was no increased risk of breast cancer. Another study, by the Institute of Child Health at University College London, which involved over 250,000 British women undergoing IVF between 1991 and 2010, also found no increased risk of breast or uterine cancer in those patients. However, they learned that IVF patients had a slightly higher risk of ovarian cancer – 15 in 10,000 odds, as compared to women who had never undergone IVF, who had 11 in 10,000 odds.

So as a consensus, from the studies quoted above and others like them, you can rest assured that fertility drugs like Clomid do not increase your risk of developing breast or uterine cancer. However, because infertility itself is a cancer risk factor, it is best that you undergo the necessary follow-up after your infertility diagnosis.

Should you have any concerns on the medications and treatments for infertility, please don’t hesitate to speak to your infertility consultant.

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Endometrial scratching to improve IVF success rates

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Endometrial scratching to improve IVF success rates

Couples who are struggling with infertility often seek In-Vitro Fertilisation (IVF) treatment in order to improve their chances of starting a family. But what happens when you have gone through multiple unsuccessful IVF cycles? Is there something else you can try?

Many patients who’ve experienced this first hand, have asked me this question, eager to try out something new to enhance their chances in the next IVF cycle. Therefore, today, I’d like to tell you more about a procedure called endometrial scratching, which has become increasingly popular in recent years.

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What is it?

Endometrial scratching is a procedure that involves agitation of the endometrium, which is the mucus membrane that lines the uterus. For conception to occur, a fertilised egg has to successfully implant itself into the wall of the uterus. Sometimes, implantation fails, usually due to the quality of the embryo or the receptivity of the endometrium. In endometrial scratching, a fertility specialist passes a special thin catheter or pipille through a woman’s cervix. The pipille is then moved up and down to gently make tiny scratches or scrapes in the uterine lining.  The similar effect can also be achieved by introducing a hysteroscope through the cervix to visualised the lining of the uterus during polyps removal.

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Why is it done?

In theory, endometrial scratching is believed to trigger the uterus to repair itself and develop a new lining, which will be more receptive to an embryo implanting. While the effectiveness of the procedure needs further investigation, studies that have been done on endometrial scratching in recent years have shown encouraging results.

One such study was conducted by the University of Nottingham, UK, which involved 158 women who had undergone unsuccessful IVF procedures. The women were divided into two groups, with one group given the endometrial scratching procedure. As a result, they found the women who had undergone the scratching procedure achieved a 49% pregnancy rate, compared to 29% in the other group.

In another study involving 1000 women, presented at the annual meeting of European Society of Human Reproduction and Embryology (ESHRE), endometrial scratching is said to increase pregnancy success rates for couples trying to conceive naturally or with Intrauterine Insemination (IUI).

When is it done?

The endometrial scratching procedure is usually recommended for patients who’ve experienced multiple unsuccessful IVF cycles or Intracytoplasmic Sperm Injection (ICSI) treatment. The procedure is best performed prior to a woman’s period or right after the period. It is done before an IVF or frozen embryo transfer (FET) cycle begins.

Does it hurt?

While the endometrial scratching procedure has been described as generally painless, requiring no anaesthetic, some women do experience discomfort during and after the procedure. The pain is similar to period cramps and there may be slight bleeding afterwards. To help with possible discomfort, patients are advised to take over-the-counter pain medication about an hour before undergoing the scratching procedure.

If you’ve gone through several IVF attempts and are keen on learning more about endometrial scratching, take the next step and ask your fertility specialist if it is right for you.

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Can IVF bring on early menopause?

Can IVF bring on early menopause?

 

One of the most common question patients like to ask about IVF is that whether the treatment itself will bring on Menopause earlier. This is probably by far one of the greatest myths about IVF which we would like to clarify.

A woman’s ovaries contain immature eggs sacs known as follicles, which have the potential of developing into mature eggs. However, most of these follicles will be lost without having fulfilled their purpose.

Women are born with millions of eggs in their ovaries. These eggs are quiescent in the ovaries until the women reach the age of menarche (when they get their first menses). At that time, the eggs in the ovaries started to come up after hibernating for 10-16 years. This is due to a pulsatile release of hormones from the organs below our brain called hypothalamus and pituitary. So, at the start of our menses, our ovaries will recruit around 10-20 eggs at one go. However, after the menses, our body will only choose one egg to grow. The rest of the eggs will regress and die off. With the help of our hormones, the particular ‘chosen’ egg with grow to a certain size and maturity, and then ovulation will occur. Hence, we only release one mature egg every menstrual cycle.

But of these many follicles, only one of them will become dominant and mature. The others that do not get a chance to mature and release an egg, will simply disintegrate and be lost in a natural process called atresia. The loss of these follicles during each menstrual cycle means that several undeveloped eggs are also lost.

Therefore, throughout a woman’s reproductive life, her ovaries will release only around 400 eggs, despite being born with millions of eggs. So basically, we ‘wasted’ around 12-20 each menstrual cycle, until the day when we reach menopause, whereby there is NO eggs in our ovaries

 

So if a woman can naturally produce only one egg per menstrual cycle? How do IVF specialists harvest several eggs at once?

 

For a woman who is undergoing an IVF treatment, the use of injectable fertility drugs (hormonal drugs) will stimulate her ovaries to overcome the natural tendency of choosing one dominant egg and ‘wasting’ other eggs produced during this particular cycle. In this scenario, the hormonal injections will stimulate all the eggs recruited during this particular cycle to grow simultaneously. Once these eggs reached a certain size and maturity, they are being harvested during an egg retrieval procedure

 

When a woman undergoes IVF, she will be prescribed with injections containing FSH. The amount given will be several times higher than what her body would naturally produce. This high amount of FSH will stimulate a lot more follicles than usual and help more of them to mature into eggs. An important thing to understand is that FSH will only act on the follicles that a woman’s body will naturally produce each month. Therefore, there is no depletion of the overall egg supply. And when those eggs are harvested during an IVF treatment, they have actually been spared from atresia that would have occurred during that menstrual cycle.

 

It is also important to note, that whether or not they undergo IVF, women who struggle with infertility are usually already at risk of having poor ovarian reserve and reaching early menopause. One of the tests that can be used to detect low ovarian reserve is the Anti-Mullerian Hormone (AMH) blood test. Egg reserves and AMH levels usually decline with age and can be affected by environmental factors such as cancer treatment or ovarian surgery, as well as inherited genetic causes, endometriosis, tumors, immunological conditions and high body mass index.

 

With that in mind, studies conducted by research teams around the world, including the British Fertility Society, Queensland University, Australia, and Cornell University, US have confirmed that IVF, even with multiple cycles, does not lead to egg depletion nor early menopause.

 

Having studied hundreds of IVF patients through the years, these researchers have concluded that IVF does not affect the timing or severity of menopause symptoms. In fact, many IVF patients reach menopause at the average age of just over 50, which is comparable to most national averages and closely resemble that of their own mothers’. The studies also found that most respondents had given birth to at least one child as a result of IVF.

 

 

Double Joy, Double Trouble?

 

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The occurrence of identical twins after a single embryo transfer

Even after many years of being a doctor, it still brings me immense joy to announce to my patient that she is indeed pregnant following a successful infertility treatment. And sometimes, the happiness is multiplied, as there isn’t one, but two buns in the oven!

 

In general, it is widely known that the occurrence of multiple births is much higher following assisted reproductive technologies (ART) as compared to incidences of twins in natural or spontaneous pregnancies. This is directly related to the number of embryos transferred back to the uterus. In general, if 2 embryos are transferred back into the uterus, the chance of having twin pregnancies is around 20-30%. As we all know, twin pregnancies carries more risks to the expecting mother as well as the babies. The risks of miscarriage, bleeding in pregnancy, high blood pressure, diabetes in pregnancy, Placenta Praevias, Caesarean Sections are some of the significant obstetric risks. The babies are also at risk of preterm births, stillbirths and complications associated with preterm deliveries such as cerebral palsies.

 

Therefore, in many countries especially in the west, it is mandatory that the patients are informed of these risks before an embryo transfer. Some countries had restricted the number of embryos transferred to one. This move had significantly reduce the incidence of twins following an IVF and had reduced the economic burden associated with medical care of pregnancies associated with twins

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However, in recent years, it had been reported that there is a higher incidence of identical twins following single embryo transfer.

 

While the incidence of fraternal twins following the transfer of two embryos is an easily understandable consequence of IVF, the causes for identical twins after ART remain speculative at best. However, there is some evidence that attributes the phenomenon to the micromanipulation techniques, length of culture and culture medium used during treatment, as well as the genetics of the parents.

Identical twins, also known as monozygotic twinning or MZT, occur when an egg and a sperm unite to form a single zygote that divides into two embryos or separate individuals. It is a rare phenomenon, which occurs in only about 1% of natural conceptions. However, in assisted conceptions, the occurrence of monozygotic twinning almost doubles.

 

The splitting of the zygote into separate embryos can occur at any time during the first 2 weeks after fertilisation. However, the timing of the split will influence the type of identical twin. For example, in around 1/3 of MZT cases where the split occurs within 72 hours of fertilisation, the result is two placentas and two amniotic sacs. In the remaining 2/3 of MZT cases, the splitting occurs 4-8 days after fertilisation, resulting in one placenta and two amniotic sacs. And in about 5% of MZT cases, where splitting occurs 8-13 days after fertilisation, the outcome is one placenta and one amniotic sac. In very rare cases, the outcome is conjoined twins.

 

Although the prospect of having twins is certainly exciting, couples must also understand that twin pregnancies are considered high risk. They can lead to various pregnancy complications with long-lasting and even permanent effects for the children. These include caesarean section, premature birth, low birth weight, Twin-Twin Transfusion Syndrome (TTTS), pre-eclampsia, gestational diabetes, fetal abnormalities and congenital abnomalies. In view of the complications that can arise from a twin pregnancy, do speak to your infertility consultant about the risks involved should you have any worries.

 

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