Tag: IVF

Categories : Cancer Obstetrics & GynaecologyTags :

Possible Cancer Risk for Children Born from Frozen Embryos

On By ModernMedia
Photo by Pavel Danilyuk

A new study suggests the possibility that children born after use of a fertility procedure known as frozen-thawed embryo transfer may have a slightly higher risk of cancer than children born through other means. The researchers presented their findings in PLOS Medicine.

In assisted reproductive technology (ART) a doctor may immediately transfer a fertilised embryo to the uterus, or, in a practice that is increasing worldwide, the embryo might be frozen and later thawed before implantation. Prior research suggests that children born after frozen-thawed transfer may have higher short-term risk of certain medical issues than children born after fresh embryo transfer. However, potential long-term medical risks have been less clear.

To better understand these risks, Nona Sargisian of the University of Gothenburg, Sweden, and colleagues analysed medical data from nearly 8 million children in Denmark, Finland, Norway, and Sweden. Of these, 171 744 were born after the use of ART, and of these, 22 630 were born after frozen-thawed transfer.

Analysis showed that children born after frozen-thawed embryo transfer were at higher risk of cancer than children born after fresh embryo transfer and those without ART. When analysed as a single group (ie, those born after frozen-thawed transfer and fresh embryo transfer), however, the use of any type of ART did not have an increased risk of cancer. The most common types of cancer seen in this study were leukaemia and tumours of the central nervous system.

The researchers stress caution in interpreting the results due to the low number of cancer cases (48) in children born from frozen-thawed embryo transfer.

Nonetheless, the findings may raise concerns about frozen-thawed embryo transfer. Future research will be needed to confirm a possible link between the procedure and increased risk of cancer, as well as any biological mechanisms that may underlie such risk.

Coauthor Ulla-Britt Wennerholm added, “A higher risk of cancer in children born after frozen-thawed embryo transfer in assisted reproduction, a large study from the Nordic countries found. The individual risk was low, while at a population level it may have an impact due to the huge increase in frozen cycles after assisted reproduction. No increase in cancer was found among children born after assisted reproduction techniques overall.”

Source: EurekAlert!

Categories : Obstetrics & GynaecologyTags :

Good Vaginal Microbiota Makeup for IVF can Happen without Probiotics

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Pregnant with ultrasound image
Source: Pixabay

The vaginal microbiota makeup can affect IVF success, and probiotics have attracted interest as a means of improving it. However, a new study presented at the 38th Annual Meeting of ESHRE shows that probiotics failed to make an impact in the microbiota composition – but a third of patients spontaneously improved within three months anyway.

Previous studies have shown that pregnancy and live birth rates are higher among women whose vaginal microbiota is dominated by lactobacillus. Conversely, those with an imbalance, or dysbiosis, where lactobacillus concentration is too low may have a lesser chance of an embryo implanting in the uterus.

Now, a new study has concluded that probiotics do not improve unhealthy vaginal flora when administered vaginally in a daily capsule to patients for 10 days before fertility treatment. No significant difference was observed between these women and those taking a placebo.

However, more than a third (34%) of all women who took part in the trial showed an improvement between a month to three months later, regardless of whether they took a probiotic or not.

On this basis, the authors suggest that it may be worthwhile to postpone fertility treatment among patients with an ‘unfavourable’ vaginal microbiome until a normal balance is achieved.

Principal investigator Ida Engberg Jepsen from The Fertility Clinic at Zealand University Hospital, Denmark, presented the findings at the 38th Annual Meeting of ESHRE. She said that the “spontaneous” improvement rate observed among patients may provide grounds for a change in approach towards IVF timing.

She added: “The study indicates that administering vaginal lactobacilli probiotics may not improve a suboptimal vaginal microbiome.

“However, a spontaneous improvement rate over a period of one to three months may provide the basis for an alternative therapeutic approach. The strategy would involve postponing fertility treatment until spontaneous improvement occurs, but further research is needed. The specific vaginal probiotic tested in this study had no effect on the favourability of the vaginal microbiome before IVF. But probiotics in general should not yet be discounted.”

The study recruited a total of 74 women with abnormal lactobacillus profile referred for IVF treatment. The women were randomised either to receive vaginal probiotic capsules (n = 38) or a placebo (n = 36). Samples were taken to determine the effect on the vaginal microbiome following the 10-day course of probiotics, and again in the subsequent menstrual cycle (on cycle day 21 to 25). Improvement in the vaginal microbiome was defined as a shift in receptivity profile from low to medium; low to high; and from medium to high.

Results showed that the vaginal microbiome improved by 40% in the placebo group and by 29% in those taking the lactobacillus probiotic. This did not represent a significant difference. Similar outcomes were observed in the menstrual cycle after intervention.

The authors advise that only two strains of lactobacilli were contained in the probiotic samples. In addition, they say the broad categorisation of the vaginal microbiome profile may not capture ‘more subtle changes’ that could affect fertility.

Source: European Society of Human Reproduction and Embryology

Categories : Obstetrics & Gynaecology TransplantsTags :

Uterus Transplants are Safe and Effective, Study Finds

On By ModernMedia
Photo by Jonathan Borba on Unsplash

The world’s first complete study of living donor uterine transplantation, published in the journal Fertility and Sterility, has found that it is an effective, safe method to remedy infertility when a functioning uterus is lacking.

After seven of the study’s nine transplants, in vitro fertilisation (IVF) treatment ensued. In this group of seven women, six (86%) became pregnant and gave birth. Three had two children each, making the total number of babies nine.

In terms of what is known as the ‘clinical pregnancy rate’, the study also showed good IVF results. The probability of pregnancy per individual embryo returned to a transplanted uterus was 33%, about the same as for typical IVF.

Participants followed up

Few cases were studied, the researchers observed, but the material is the world best and included extensive, long-term follow-ups of participants’ physical and mental health.

None of the donors had pelvic symptoms but, in a few, the study describes mild, partially transient symptoms in the form of discomfort or minor swelling in the legs.

After four years, health-related quality of life in the recipient group as a whole was higher than in the general population. Neither members of the recipient group nor the donors had levels of anxiety or depression that required treatment.

Growth and development of the children were monitored as well, up to age two and is, accordingly, the longest child follow-up study conducted to date in this context. Further monitoring is planned to adulthood.

Good health in the long term

“This is the first complete study that’s been done, and the results exceed expectations in terms both of clinical pregnancy rate and of the cumulative live birth rate,” said study leader Mats Brännström, professor of obstetrics and gynaecology at Sahlgrenska Academy, University of Gothenburg.

“The study also shows positive health outcomes: The children born to date remain healthy and the long-term health of donors and recipients is generally good too.”

The first birth after uterine transplantation took place in Gothenburg in 2014. Another seven births followed, within the framework of the same research project, before anyone outside Sweden gave birth following uterine transplantation.

The research group has since passed on its methods and techniques through direct knowledge transfer to several research centres outside Sweden. By the end of 2021, there were an estimated 90 uterine transplants worldwide, of which 20 had been done in Sweden. Worldwide, some 50 children have been born after uterine transplantation.

Source: University of Gothenburg

Categories : GeneticsTags :

Mice Born From Stem Cell-derived Gametes

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Photo by Kanashi on Unsplash
Photo by Kanashi on Unsplash

For the first time, mice have been born from gametes that have been created entirely from stem cells, marking the beginning of a revolutionary new reproductive option.

The experiment is the brainchild of Dr Katsuhiko Hayashi of Kyushu University, who has led the pursuit of making gametes outside of a living body. If adapted for humans, these wild reproductive pursuits are bound to shake up our entire conception of the beginning of life, similar to the way “test-tube” babies did when in vitro fertilisation (IVF) was first introduced.

Dr Hayashi dreams of even bigger possibilities; since stem cells can be rapidly created from skin or other cells, they are an endless source of raw material to make sperm and egg cells. These gametes, if fully functional, can merge into a zygote inside a test tube, be transplanted into a surrogate, and birth a new generation without ever seeing testes or ovaries.

Though still far off for humans, in vitro gametogenesis, or IVG, has great potential. Researchers can use these lab-grown models to better understand how reproductive cells form and mature. For couples struggling to conceive, or people who’ve lost reproductive function due to diseases like cancer, IVG would offer a new route towards pregnancy. Same-sex couples could also potentially conceive children with their own genetic makeup. There are many possibilities, and a wide range of ethical problems.

The basis of the technology uses induced pluripotent stem cells (iPSCs), which can be nudged in any direction, including sperm and egg. Back in 2011, Dr Hayashi showed that by bathing stem cells in a particular chemical soup, his team was able to produce sperm cell precursors, with the capacity to turn into functional sperm.

In 2016, the team achieved the same with eggs in mice, mimicking the entire process of how ovaries make eggs – which were used to produce healthy pups. However, eggs made in a test tube couldn’t develop naturally outside the ovary. Fresh ovarian tissue from mice was needed, creating an obvious challenge for fertility treatments in humans.

In the current study, the team focused on the support cells that normally encapsulate a developing egg. These support cells thrive inside the ovary, secreting hormones and nutrients that help support the metabolic needs of an egg  – a crucial step, which includes forming ovarian follicles for the eggs to mature in.

These ovary-supporting cells can also be made from stem cells if the right chemical keys are used, and so after five years Dr Hayashi figured out those keys. Many of them sport fanciful names like ‘sonic hedgehog‘ (SHH), but most of these proteins belong to the morphogen family, in that they can morph the physical structure and identity of a tissue.

After dousing stem cells with this soup, the cells differentiated into foetal ovary supporting cells, with a gene expression profile closely mimicking that of their natural counterparts.

Next, the researchers added precursor immature egg cells, also made from stem cells. Together, the cells coalesced into tiny ovarian follicles, with support cells forming a bubble wrapping the developing egg. The eggs were then fertilised with sperm, transplanted into surrogate mouse mothers, and after normal pregnancies, resulted in about a dozen healthy pups. Those mice eventually gave birth to babies of their own.

The artificial ovary produces mature eggs less effectively than its natural counterpart, suggesting there’s still much to be learned about this stage of reproduction.

Application of this technology to assisted reproduction in humans is still decades away: human reproductive cells take far longer to mature than those in mice, and likely require different supporting nutrients for the sperm, egg, and surrounding tissue.

The team is now testing their chemical soup in marmosets, to be followed by primates.

Currently no laws or ethical frameworks deal with IVG, since the technology is so new.

Dr Hayashi is taking it step by step, and welcoming public discourse before even considering any clinical use. The first step, he said, is verifying the quality of the stem-cell derived eggs, adding, “That could take a long, long time.”

Source: SingularityHub

Categories : Obstetrics & GynaecologyTags :

‘Far Too Many Oocytes’ Being Extracted in IVF

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Photo by MART PRODUCTION from Pexels

A study has suggested that IVF clinics in the UK may be retrieving “far too many oocytes” and that most of them “may never be used and are probably discarded”, a finding that may well represent global practice.

Studies indicate that the optimal and safe number of oocytes needed for achieving an ongoing pregnancy is between six and 15. However, the use of egg freezing (such as to preserve fertility to a later age, known as social egg freezing), frozen embryo replacement (FER) cycles and aggressive stimulation regimes has raised this number in order to boost success rates in older women and in poor responders who produce fewer eggs. What is not known is the impact of numbers of eggs retrieved and of over-stimulation practices on the health of patients, and on their emotional state and finances.

Details of the analysis were presented online at the virtual Annual Meeting of ESHRE by Dr Gulam Bahadur from North Middlesex University Hospital, London.

More than 1.625 million eggs in the UK were retrieved from 147,274 women between 2015 and 2018. Although an average of 11 eggs was collected per patient, 16% of cycles were associated with 16-49 oocytes retrieved (per cycle) and 58 women each had over 50 eggs collected in a single egg retrieval procedure.

“Our observations suggests that the high oocyte number per retrieval procedure needs re-evaluation,” said Dr Bahadur. “In particular, this needs to focus on the side effects, including ovarian hyperstimulation syndrome and procedure-related complications, and on the fate of unused frozen oocytes and the costs associated with freezing them.

“Patients should be advised that it’s better to collect fewer eggs leading to good quality embryos which may go to term and result in a healthy baby.”

This report is based on all UK IVF clinics and relates to non-donor fertility treatment carried out between 2015 and 2018 during which 172 341 fresh oocyte retrieval cycles took place. All outcomes and patterns remained uniform over the four years.

A substantial number (n = 10 148) of cycles did not yield any oocytes. Over half (53%) of all IVF cycles were in the desired egg yield range of 6-15. In addition, a quarter of cycles yielded 1-5 eggs; 14% produced 16-25; and a minority (2%) resulted in 26-49 oocytes. The authors point out that multiple birth rates increase significantly from 6-15 oocytes onwards, which increases the risk of birth complications and low birth weight.

A total of 931 265 embryos resulted from all eggs retrieved – a fertilisation rate of 57%. Of the embryos created, more than one in five (22% or 209,080) were transferred into the uterus, while a slightly higher proportion (24% or 219, 563) were frozen.

The fate of the unfertilised oocytes (43%) is unknown, though they are usually discarded. Most of the embryos not transferred (54%) will likely be discarded after patients have paid for several years of storage.

“This comes with a financial and emotional cost,” said Bahadur. “Patients build an attachment with this frozen material and there’s insufficient counselling to support them. They should be given more information about the implications of freezing eggs and embryos.”

Source: European Society of Human Reproduction and Embryology

Categories : Obstetrics & GynaecologyTags :

Rate of Twin Births At A Global High

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Image by atomicqq from Pixabay

The first comprehensive global survey of twinning has reported an enormous increase in the number of twin births around the world, but appears to be plateauing.

One main reason for the increase is that, due to IVF and other fertility services being more readily available, the number of non-identical twin births is increasing. This is due to practices such as hormone stimulation releasing multiple ova, as well as the now discouraged practice of releasing multiple embryos into the womb in IVF. A systematic review also found that with IVF, letting embryos mature before implantation is also linked to increased odds of monozygotic twins. as well as women becoming pregnant later in life – age increases the likelihood of having natural, non-identical twins, peaking at age 35 to 39.

However, instead of continuing to climb, there are signs that twin births have reached a maximum.

“The trends are really quite striking,” said Christiaan Monden, a professor of sociology and demography at Oxford University. “Over the past 40 to 50 years we’ve seen a strong increase in twinning rates in rich, developed countries, and that has led to more twins in both a relative and an absolute sense than we’ve seen ever before.”

The researchers analysed twinning rates from 2010 to 2015 in 165 countries, which covered 99% of the world’s population. In 112 of those countries, they examined further birth records for 1980 to 1985. 

Although Africa is still the leading continent for twin births, other regions are catching up. The researchers found that, since the 1980s, twinning rates have risen from 9 to 12 per 1000 births, with the greatest rise in more developed regions such as  America (71%), Europe (60%) and Asia (32%).

In the UK, twinning rates rose about 62% but are thought to have fallen since the launch of a campaign to reduce multiple births in 2007. 

Raj Mathur, the chair of the British Fertility Society and a consultant gynaecologist at St Mary’s Hospital, said: “It doesn’t surprise us that twinning rates have increased because the availability of assisted reproduction has increased and also because women are slightly older when they have their first children, and both those things will increase the twin rate.[…]

“I think we’ve reached a peak in terms of twinning rates from medical interventions, certainly in the developed world, but the spread of IVF in Africa and South America is still rather limited on a per capita basis, and there are vast numbers of sub-fertile people in Africa particularly who don’t have access to IVF.

Dr Mathur added a note of caution about IVF, as twins have more risks such as lower birth weights and higher still birth and infant mortality rates

“The challenge will be how to spread IVF to them without also giving them higher twin rates. The majority of twin babies are absolutely fine, but there is no doubt that a twin pregnancy carries greater risks for the mother and the baby, so when we can avoid it we should avoid it. The principle we follow is neatly summed up by the phrase ‘one at a time’,” Mathur said.

Source: The Guardian