Doctor in Neha Lad
Diseases which are caused by some sort of genetic mutations in the mitochondria, can be quite deadly. This is the reason why Mitochondrial Replacement Therapy, also known as Three-Person IVF is being seen as a much more desired option for those women, who carry mitochondrial mutations.
Almost all the genes in a cell remain trapped in the nucleus but a small fraction of them remain present in the mitochondria as well. During the fertilisation of eggs, the genes in the egg’s nucleus get combined with the genes in the nucleus of the sperm, which in turn creates a new cell. On the other hand, mitochondrial genes are involved in this mixing. Rather they are passed on from mother to child.
The main reason behind three-person IVF is to help find a way, so that the mitochondrial genes can be replaced in an affected cell of the egg prior to the time they get passed on to the child. This is carried out when the egg cell of the donor gets acquired and the nucleus is removed from the cell, hence leaving the cell with healthy mitochondria. After that, the mother’s nucleus, which stays unaffected, is removed and gets placed in the donor’s egg cell, thereby creating an egg cell which must contain healthy genes not only in the nucleus but also in the mitochondria.
Genes Are Complex in Nature
- Genes communicate with one another. Cells get engaged in a variety of complex processes like division of cells or respiration, which are highly unlikely to be performed only by single genes acting in an isolated manner. So a network of genes works together, with each one making a contribution of certain particular components.
- Genes tend to be variable in nature, which basically means that no two genomes are similar. Due to this reason, the result of a typical pair of genes interacting with one another will at times be different for different individuals. This is the dark side of genetics, which has not been studied in a comprehensive manner and experts are not aware of exactly how widespread this might be.
- Experts call this type of effect as Epistasis, which can occur between individual genes, between two or more sets of genes or even between whole genomes. The one occurring between whole genomes, has relevance to discuss about the safety and ethics of MRT. The reason is that, when a mitochondrial genome from a donor replaces the affected mitochondria, the parents’ nuclear DNA must communicate with a completely new genomic partner. The ethical implications related to the epistasis getting changed between nuclear DNA and mitochondrial have thus far been completely ignored.
Ethics Comes First
The review of the ethics related to MRT or Three-Person IVF came up with the conclusion that if the procedure was safe, then it could be considered as ethical. In other words, they concluded that if the trials carried out on humans showed that the treatment undertaken was safe, then it could also be considered as ethical as well.
In vitro fertilisation (IVF) is a medical procedure followed for those women or couples suffering from infertility or for certain specific genetic problem. In the normal course, women or couples experience positive results within a few IVF cycles. However, in spite of reasonable pregnancy rates, some women may require few more cycles to achieve pregnancy. In such cases, in order to ensure a healthy pregnancy, the gynecologist may suggest the women undergo Endometrial Scratching before IVF.
Endometrium explained in brief:
The uterus is located in the pelvic region and it is in the size and shape of a pear. The inner cavity of the womb or uterus is protected by the tissue lining called endometrium, also called endometrial. The endometrium plays a significant role in supporting the pregnancy.
The enhanced success of achieving pregnancy:
The endometrial scratching procedure is a very simple one, which is resorted, so as to improve the results of IVF procedure. In this procedure, the gynecologist uses a very fine catheter and makes a small scratch on the endometrial lining. In fact, the scratch causes a kind of inflammatory reaction in the uterus. This inflammatory reaction induces the endometrium to be highly receptive to embryos during the successive menstrual cycle. This added receptivity enhances the success of pregnancy during the next menstrual cycle.
Considering the higher level of success in achieving pregnancy, the endometrial scratching procedure has gained popularity in the IVF procedure. However, some of the other issues related to endometrial scratching may be as follows:
- Endometrial scratching optimises the uterine lining and thereby, makes it easier to continue the embryo implanting procedure. Normally, before the endometrial scratching procedure, the gynecologist may suggest endometrial biopsy.
- The endometrial procedure is usually suggested for those women who had two or more unsuccessful IVF procedures, despite having good quality embryos. However, in some cases, depending on the health of the patient and various other factors, the gynecologist may suggest this endometrial scratching at the very first IVF procedure. This procedure can be availed either for fresh embryos of the couple or frozen embryos or for the donor egg.
- Although this is a part of a surgical procedure; endometrial scratching is very simple and painless and it is done without administering anesthesia. The procedure does not require any hospitalisation. In fact, the patient can go home soon after the procedure. Except for a few pain killers, this procedure does not require any extensive medication.
This is a safe and easy procedure. Neither does it lead to any side effects, nor is the procedure burdensome for your wallet. Many couples have been benefited by this endometrial scratching procedure.
The available eggs in the ovaries at a time are collectively called an ovarian reserve. Low reserve happens when the production of eggs reduces. This affects the chances of pregnancy. The general cause of low reserves can be aging ovaries. In such cases, the ovary may be healthy and functioning even if the reserve is low. Production of eggs lower as a woman ages. A woman starts with 250,00 to 500,000 eggs at puberty and ends up with 1000 eggs at menopause.
Low reserves are caused by
- Production of eggs decreases: Chromosomal abnormalities like Turner syndrome (lack of two X chromosomes) and genetic anomalies like Fragile X can decrease egg production.
- Ovarian tissue damage: Rough torsion, endometriosis triggered ovarian cysts, malignant or benign tumours, surgical removal of ovary or any other part of it, chemotherapy or radiation, pelvic adhesions, immunological problems or high BMI (Body Mass Index) can destroy the ovarian tissues.
If a woman has low ovarian reserves, then she will be put on the either of the following protocols:
- Short GnRHa Flare: Gonadotrophin releasing-hormone-agonist (GnRHa) like Lupron, Nafarelin, Synarel or Buserelin is administered. This therapy is initiated at the onset of menstruation. The goal of the treatment is to stimulate the release of the follicular stimulating hormone (FSH) which augments the ovarian follicular growth.
- Combined Clomiphene or Gonadotrophin/Letrozole Stimulation: Older women are mostly administered this protocol. But it is strongly advised not to, as this protocol can potentially harm the egg or the embryo.
- Mid-follicular GnRH-antagonist protocol: Once the GnRHa-agonist protocol is commenced, the GnRH-antagonist is given several days later. Once the follicles reach the size of 12mm, GnRHa antagonists like Ganirelix, Orgalutran, Cetrotide and Cetrorelix are added. These drugs stop the pituitary from secreting the luteinizing hormone (FSH leads to secretion of this hormone).
- Long GnRHa Pituitary Down Regulation Protocol: This is the usual approach to deal with low ovarian reserves.
- Agonist/Antagonist Conversion Protocol: This protocol inhibits FSH production. This protocol generally yields good results.
The success rates of IVF are in the spotlight but there is worry among patients. IVF cycles are extremely costly and so if things don’t work out at one go and women require more cycles for getting the desired success, then that means, you would need to spend a lot.
The problem lies on the fact that clinics are not bound to disclose the kind of success rates they have, so this makes it impossible for anyone to compare each and every clinic. So, how to make sure that you get down to a genuinely good IVF Clinic, where there is surety that going through an IVF cycle would not let your money go in waste.
- Pregnancy against live birth rates: There is a steady decline not only in woman’s fertility but also in the success rates of IVF, as they grow older. In case of almost all clinics, the success rates tend to be on the higher side for those women, who are under the age of 30, with them having 26% chance that they are going to take home a baby after going through each cycle of IVF. On the other hand, those are aged above 40 years have just about 6% chance of getting success and take a baby home. Generally, figures suggest that only half of the pregnancies through IVF, for women above the age bracket of 40 years will lead to live birth. So, it is important to take note, if you see on the website of any clinic that they are showing pregnancy rate rather than live birth rate, most importantly if you are in your 40s. Prospective patients must ask their clinic to disclose the pregnancy rate as well as the live birth success rate for their respective age groups.
- Blastocyst cultures: Another way through which one can easily predict the success of any particular clinic is by seeing whether they use blastocyst culture. The normal tradition was to grow embryos just for a few days till the stage of cleavage but now, the main aim of most treatment is to the growth of embryos for five days till they reach the stage of a blastocyst.
- This is a kind of a situation wherein the best survive till the end and the weaker ones tend to die down. This process of selection makes it easier for embryologists to take the best embryo for transfer, hence leading to better results.
- Sperm injections: Success through IVF is also dependent upon the cause behind infertility. Some male counterparts have really low sperm count and hence require intra-cytoplasmic sperm injection. This leads to injection of an individual sperm into an egg. At times when things are not clear whether a patient would need ICSI, doctor will generally allow half of the eggs to get inseminated through standard process of insemination and the other half would be injected through ICSI. If someone gets enough eggs, then it would surely require to enquired.
Of a million sperms released in one ejaculation, a single sperm manages to fertilize the egg, which grows into an embryo and then a baby. Due to various reasons, when this does not happen, it is termed as infertility and is currently on the rise.
With IVF, couples sometimes go through multiple sessions to ensure fertilization. ICSI or intracytoplasmic sperm injection improved this chance of fertilization. It is where a single sperm is used to fertilize an egg in an artificially controlled environment and then injected into the uterus where it grows further.
The next step in this technique is IMSI, where the chances of successful pregnancy are further enhanced and also promises improved quality of the embryo. IMSI, as it stands for, has “morphologically selected” which means under a highly powerful microscope, the best sperms are selected and then used to fertilize the egg. Morphology stands for shape, and the shape of the sperm is a direct indicator of the sperm quality. This not just ensures good success rate but also ensures the sperm which is used produces a high-quality embryo.
- High success rate of fertility
- Reliable and efficient method of ART (assisted reproductive technology)
- More expensive than traditional IVF methods or ICSI
- Requires complex equipment, training, and set-up
- Useful in couples who have failed IVF previously
- Male infertility with unidentifiable cause
- Poor sperm quality
What to expect?
Both partners are prepared both physically and mentally prior to IMSI.
Before the procedure - men:
- A screening is first done to decide if the sperms can be used directly
- In case of hereditary diseases, a donor is preferred
- The first technical step involves sperm collection, either directly or through a donor
- Sperms are collected either through masturbation or through a small incision in the testicles
- Sperms used could be fresh or frozen; fresh ones may be stored for later use also
Before the procedure – women:
- The woman is put on some ovulation therapy to ensure the release of multiple eggs, so a good one is picked. These high doses of hormones ensure multiple eggs are released.
- Egg release is monitored through blood and urine tests
- They are collected within after 36 hours of release
During the IMSI procedure:
- A healthy egg is chosen and placed in a glass container containing hyaluronidase
- Sperms are placed in a medium which will slow their movement, which enables picking a good sperm for fertilization
- The dual advantage of this is that in addition to a high success rate of fertilization, the quality of the embryo is also assured
A landmark development, which could help widen the scope of fertility treatments, has been achieved through the growth of human eggs from the nascent stage to full maturity outside the body.In UK, one out of six couples face fertility problems and so the question is that whether this development in any way offer some hope to all those people.
The majority of the opinion is that it presents an important step in the right direction but the general progress in research into the very basic secrets, related to the origin as well as the creation of life, gets measured by decades more than years.
For instance, around 66 percent of women, who are under the age of 35, undergoing in-vitro fertilisation treatment, will not conceive a baby after going through their treatment cycles. Specialists are not sure about the fact that why most of the IVF treatments fail but the development leading to advancement of knowledge along with the study of human eggs, which are grown in lab, could surely be encouraging signs for boosting rate of success in IVF.
The rate of success achieved through IVF treatment may give disappointing number but thankfully, due to the research, they are around 85 percent that what they were in 1991. A similar kind of pattern might be followed while transforming human eggs which are lab-grown into feasible treatment procedures. The research was carried out by one Professor named Evelyn Telfer and colleagues at Edinburgh University, the Royal Hospital for Sick Children, Edinburgh and the New York Center for Human Production.
Ten women, who were undergoing caesarean-section births had donated their eggs, which were grown from ovarian tissue.The research had gone on to provoke some tough questions, like why did few of the developed eggs mature in only 22 days in comparison to the five months, which it would have normally taken in the body and also why only 10 per cent of the eggs reach full maturity. The idea of the lab-made eggs attaining maturity should be same as that of the natural cycle was challenged by Professor Telfer. He had given out his argument that the fact it takes longer in the body because eggs have to work simultaneously with the hormonal cycle of a woman, which consists of a number of control mechanisms within the body.
Opinion of the ProfessorThe professor opined that he would like to describe the way eggs tend to grow outside the body in their system not as any kind of accelerated development but it is to be seen as development without any brake being put into it. As far as the logic goes, he felt that there was no concrete reason why human eggs should take a number of months to mature.He had also gone on to say that the main problem was the lack of basic knowledge about human eggs. Lack of progress made by IVF in the last 40 years is mainly due to the lack of understanding about the fundamental aspects of how human egg develops. He even believed that this kind of research work would allow them to give the necessary insight which they need. In case you have a concern or query you can always consult an expert & get answers to your questions!
Suffering from the problem of infertility can be a heartbreaking as well as a very frustrating process but still with different kinds of IVF treatments available today, a lot of women can realize their dreams of having their own family. In Vitro Fertilization is a laboratory procedure where the sperm and egg are fertilized outside the body. It has been more than 35 years since the first baby was born through this process of IVF and now it has become the go-to method for treatment regarding reproduction, which assists in the birth of over 5 million babies. With the availability of different kinds of IVF treatments currently, to navigate one’s way through the in vitro fertilization process can seem to be quite confusing as well as intimidating.
Now, we take a look at the difference between the types of IVF treatments and see if they are right for a woman.
Different Types of IVF
Since the time IVF came into being, more than three decades ago, it has become the leading form of assisted reproduction, having an estimated amount of 70000 babies per year getting conceived through this procedure. The procedure of IVF involves a really complex series of procedures where an egg gets removed from the ovaries of a woman and fertilized with sperm in a laboratory. The fertilized egg, which is called an embryo then, gets returned to the womb of the woman for its growth and development.
Natural Cycle IVF: Natural Cycle IVF bears similarity with the standard IVF treatment but this takes place without having to use medication for stimulating the ovary leading to the preparation of multiple eggs. Natural IVF basically monitors the ovulation cycle of a patient with the intention to retrieve only one egg. This is unlike conventional IVF, which requires retrieval of multiple eggs. Women who opt for Natural IVF due to the process being more economical compared to the traditional treatment. Natural Cycle IVF requires less time as compared to the traditional one and is thought to be a safer as well as stress-free treatment option by certain experts.
Mini IVF: Minimal Stimulation IVF or Mini IVF is a kind of IVF, which is supposed to be somewhere between Natural IVF and Traditional IVF. The Mini IVF treatment is different from the Traditional IVF, with regard to how it gets administered through medicines. In case of Mini IVF treatment, less amount of medication gets administered by the specialists, so that there can only be production of two to three eggs at a time, in comparison to 10 or more in case of conventional IVF.
At the time of treatment, the retrieval of eggs and fertilization take place just like they are done in any other IVF process. The only difference lies in the stimulation part, which is lot less in this case compared to regular In Vitro Fertilization. Despite Mini IVF being suggested as a gentler approach to IVF, some researchers feel that less number of eggs might reduce the possibility of getting success.
Despite the positives, certain fertility experts send out a warning due to the significantly low chance of pregnancy with this process. In case you have a concern or query you can always consult an expert & get answers to your questions!
Babies who are born through IVF, have greater risk of developing heart related problems as researchers believe that manipulation of nature in this manner is ought to have some adverse results. There were some Swiss scientists, who had compared 64 children taking birth through IVF techniques and 57 children taking birth in natural manner, found that among those 64 children, 30% of them had high pulmonary arterial pressure and greater amount of rigidity in the blood vessel at high altitude.
While considering all the things, the parents who have gone through IVF should not be concerned. To a large extent, IVF has ensured that parents get healthy children. Now, if IVF goes ahead to signal a problem, then it will suggest that all those children would have premature heart disease when they attain the ages of 50s and 60s, rather than in their 70s and 80s. Now, if one compares the premature heart disease with the gift, IVF presents parents with newborn babies, then in that regard, none of the parents should be too concerned at the moment.
A Swiss research team, which has been led by scientists at Bern University Hospital, is of the opinion that the increased risk of heart problems in latter half of life is a result of chemical processes, till the time, the embryo still remains in the Petri dish. The expression of some genes tends to get influenced by the chemicals in the cultures. The team members had pointed out that a lot of non-IVF people also tend to have the same kind of genetic markers.
One of the researchers said that they could not come to any conclusion about the study of 65 IVF children. At the time of IVF, doctors get hold of an egg from the ovaries and then they co-incubate that with sperm in the test tube. They can even directly inject a sperm into the egg to help with the process of fertilization.
One of the professors claimed that this particular phase was an extremely critical phase of development. The first ten days after sperm and the egg collide to form an embryo, a lot happens for determining normal health and then even slight bit of changes in the chemical as well as the physical environment can lead to important developmental changes in babies at the end of gestation period.
The cellular stress which the embryos could experience, might well be caused by a couple of reasons: The physical stress of getting lifted, injected or manipulated and the other reason could well be the chemical stress related to chemicals within the environment of the test tube or modifications in the level of oxygen.
As the study was relatively small, so it did not come up with conclusive evidence if babies born through IVF would suffer heart problems in the form of heart attacks or strokes. The study does indicate that in all likelihood a person will have high blood pressure, diabetes and possible heart attack or stroke in the middle age. The ideal precaution would be to take all possible healthy measure, with regard to diet, exercise and check-ups on a regular basis. In case you have a concern or query you can always consult an expert & get answers to your questions!