IVF

Dienogest for endometriosis

Dienogest for endometriosis

A study in the Journal of Obstetrics and Gynaecology found that dienogest was effective in decreasing the size of endometrioma and reducing endometriosis-associated pain, along with a favorable safety and tolerability profile.

The prospective study from Turkey recruited 30 patients diagnosed with endometrioma at Erciyes University Medical Faculty Hospital in Kayseri, Turkey, between November 2015 and September 2016.

Only 24 patients were included in the study because three patients were unable to complete the dienogest therapy due to menstrual irregularities, two patients did not attend to regular controls, and one patient was operated on at another hospital.

The mean age of the 24 patients was 29.58 years, with a mean body mass index (BMI) of 25.9. The endometriomas in 86.67% of the patients were unilateral.

Patients were instructed to take a single daily 2 mg dose of the synthetic oral progestogen continuously through the 6-month study period, preferably at the same time each day.

Patients were examined for efficacy and side effects at baseline, 3 months and 6 months.

The mean volume of the endometrioma decreased a significant 41% from 112.63 ± 161.31 cm³ at baseline to 65.47 ± 95.69 cm³ at 6-month follow-up (P = 0.005).

A visual analog scale (VAS) from 0 to 10 (0: no pain, 10: unbearable pain) for pelvic pain also decreased significantly from 7.50 to 3.00 at 6 months after treatment (P < .001).

The most common side effect was abnormal vaginal bleeding, consisting of prolonged and frequent uterine bleeding or spotting (16.6%), followed by weight gain (8.3%), headache (8.3%), depressed mood (8.3%), dizziness (4.1%) and libido reduction (4.1%).

Laparoscopic excisional surgery for endometrioma is currently the most valid approach in the treatment of endometriomas,” wrote the authors. “However, there are concerns about ovarian reserve damage during surgery.”

Because there is no consensus on the timing of surgery in young women and whether surgery should be delayed in infertile women planning in vitro fertilization (IVF), strategies to eliminate or decrease the size of ovarian endometriomas without affecting a young woman’s fertility potential need to be designed, according to the authors.

One potential solution is presurgical administration of a gonadotropin-releasing hormone agonist (GnRH agonist), which renders conservative laparoscopic surgery easier for endometriosis and might reduce postsurgical damage to ovarian function by reducing active inflammation, adhesion of endometriotic lesions and the size of the endometrial cysts.

However, GnRH agonist therapy causes adverse effects by the deficiency of the ovarian hormone, such as an irregular menstrual period, hot flashes, vaginal burning, decreased sexual interest, and bone mineral density loss.

On the other hand, dienogest for IVF patients with an endometrial cyst prior to oocyte pick-up might facilitate oocyte pick-up and prevent bacterial infection post-procedure.

Long-term use of dienogest in younger patients with endometriomas who are yet to give birth may reduce the possibility of surgery by reducing the size of the endometriomas and may preserve ovarian reserve,” wrote the authors.

In addition, dienogest could reduce the incidence of infectious complications from pelvic abscess after oocyte retrieval and from surgical procedures for infertile patients with endometrioma.

The authors said clinicians should consider dienogest prior to initiation of an IVF cycle to reduce endometrioma size.

Read more: https://pubmed.ncbi.nlm.nih.gov/33629621/

Researchers isolate high-quality sperm using acoustic waves

Researchers isolate high-quality sperm using acoustic waves

Monash University researchers have combined acoustic waves and fluid dynamics to create a new approach for separating high-quality sperm in assisted reproduction – opening new windows for infertile couples to have a family of their own.

This rapid and automated acoustofluidic process, developed by a team from Monash University’s Department of Mechanical and Aerospace Engineering, can isolate sperm with normal head morphology and high DNA integrity from raw semen samples.

The device can process roughly 140 sperm per second and select more than 60,000 high-quality sperm in under 50 minutes – a clinically-relevant number of sperm to perform IVF (In Vitro Fertilisation) and ICSI (Intracytoplasmic Sperm Injection).

This life-changing research, published in the leading microfluidic journal Lab on a Chip, was led by second-year Ph.D. student Ms Junyang Gai. The work has been supervised by Dr Reza Nosrati and Professor Adrian Neild – experts in microfluidics from the Department of Mechanical and Aerospace Engineering.

The approach isolates sperm from raw semen by applying an acoustic field at a 30° angle to the flow direction. The acoustic forces direct and push high-quality sperm out of the mainstream, across the microchannel and isolates them in a separate outlet, leaving the general population of sperm in the raw sample.”

With the application of SSAW (standing surface acoustic waves) at 19.28 MHz and 1-2W, the acoustic radiation force was large enough to overcome the drag and guide the motile sperm to swim across the microchannel width, while other sperm and debris followed the mainstream flow to be collected from the discarded outlet.

This enabled a continuous, high-throughput, and size-dependent selection process for isolating high-quality sperm.

“Our results demonstrate that the selected sperm population exhibit a considerably higher percentage of progressively motile sperm (83 per cent), than both the initial raw sample (52 per cent) and the discarded subpopulation of sperm (36 per cent),” Ms Gai said.

The result is the selection of sperm with over 60 per cent improvement in progressive motility (the ability for sperm to move independently), while providing a clinically-relevant sample for IVF and ICSI. Sperm selected from this approach also show a near 40 per cent improvement in DNA integrity.

Dr Nosrati says the success rate depends on many different parameters, but ultimately, it is down to the quality of sperm and egg.

“Our process aims to select better sperm within a faster time frame, so hopefully this can lead to improved outcomes in assisted reproduction. When fully tested and implemented, this method could open new windows and opportunities for infertile couples to have a baby,” Dr Nosrati said.

“We hope that with further testing, our acoustofluidic sperm selection process can provide new opportunities and be of benefit to the assisted reproduction industry, and help remove the fear, anxiety and negative stereotypes associated with infertility.”

The infertility rate has increased over the past 50 years, with one in six couples experiencing infertility. Male infertility is responsible for about 30 per cent of cases, with a combination of male and female factors contributing to about half of cases, worldwide.

“Male infertility is a global reproductive issue and several clinical approaches have been developed to tackle it. However, their effectiveness is limited by the labour-intensive and time-consuming sperm selection procedures used,” Dr Nosrati said.

Sperm preparation or selection is a key step in assisted reproduction being performed right before fertilising the egg.

The current clinical process involves multiple washing and centrifugation steps and a manual selection step, and takes up to three hours to complete, which can also be harmful to sperm.”

Professor Neild says the method of sperm selection hasn’t changed much over the past 30 years, selecting sperm mainly based on motility, and as a result, the success rate of assisted reproduction cycles has plateaued at about 33 per cent.

“Our approach also considers sperm size and morphology during the selection process, in addition to sperm motility. With further research, hopefully our approach can improve the outcomes of assisted reproduction and reduce the costs associated with the treatment cycle,” Professor Neild said.

Professor Neild is a world expert in acoustofluidics with many important contributions to the field over the past 15 years. Dr Nosrati is a pioneer in microfluidics for assisted reproduction and has developed technologies for sperm selection and analysis over the past six years.

Read more: https://pubs.rsc.org/en/content/articlelanding/2020/LC/D0LC00457J#!divAbstract

System trained to detect highest quality IVF embryos outperformed trained embryologists

System trained to detect highest quality IVF embryos outperformed trained embryologists

In-vitro fertilization (IVF) can offer a life-changing solution to infertile couples. But the average success rate for IVF is about 30 percent.

Investigators from Brigham and Women’s Hospital and Massachusetts General Hospital are developing an artificial intelligence system with the goal of improving IVF success by helping embryologists objectively select embryos most likely to result in a healthy birth.

Using thousands of embryo image examples and deep-learning artificial intelligence (AI), the team developed a system that was able to differentiate and identify embryos with the highest potential for success significantly better than 15 experienced embryologists from five different fertility centers across the United States.

Results of their study are published in eLife.

“We believe that these systems will benefit clinical embryologists and patients,” said corresponding author Hadi Shafiee, PhD, of the Division of Engineering in Medicine at the Brigham. “A major challenge in the field is deciding on the embryos that need to be transferred during IVF. Our system has tremendous potential to improve clinical decision making and access to care.”

Currently, the tools available to embryologists are limited and expensive, and most embryologists must rely on their observational skills and expertise. Shafiee and colleagues are developing an assistive tool that can evaluate images captured using microscopes traditionally available at fertility centers.

“There is so much at stake for our patients with each IVF cycle. Embryologists make dozens of critical decisions that impact the success of a patient cycle. With assistance from our AI system, embryologists will be able to select the embryo that will result in a successful pregnancy better than ever before,” said co-lead author Charles Bormann, PhD, MGH IVF Laboratory director.

The team trained the AI system using images of embryos captured at 113 hours post-insemination. Among 742 embryos, the AI system was 90 percent accurate in choosing the most high-quality embryos.

The investigators further assessed the AI system’s ability to distinguish among high-quality embryos with the normal number of human chromosomes and compared the system’s performance to that of trained embryologists.

The system performed with an accuracy of approximately 75 percent while the embryologists performed with an average accuracy of 67 percent.

The authors note that in its current stage, this system is intended to act only as an assistive tool for embryologists to make judgments during embryo selection.

“Our approach has shown the potential of AI systems to be used in aiding embryologists to select the embryo with the highest implantation potential, especially amongst high-quality embryos,” said Manoj Kumar Kanakasabapathy, one of the co-lead authors.

Read more: https://elifesciences.org/articles/55301

Frozen IVF embryos do not increase chance of pregnancy

Frozen IVF embryos do not increase chance of pregnancy

The use of frozen rather than fresh embryos in IVF does not increase the chance of a successful pregnancy, newly published data shows.

The findings discourage the ‘freeze-all’ strategy adopted by some fertility clinics in recent years. They thought that using frozen embryos rather than immediately transferring fresh embryos to the uterus allows patients’ bodies more time to recover from disruptive hormonal treatment required in IVF and intracytoplasmic sperm injection (ICSI) cycles.

Preliminary results of the randomised, multi-centre trial were reported last year at the European Society for Human Reproduction and Embryology’s annual meeting. Speaking at the meeting, lead author Dr Sacha Stormlund from Hvidovre University Hospital in Copenhagen, Denmark, remarked: ‘I think we can now reasonably say, based on our results and those from other recent trials, that in normally ovulating patients there is no apparent benefit from a freeze-all strategy in IVF.

The study, recently published in the British Medical Journal, analysed 460 IVF and ICSI patients across Denmark, Sweden and Spain.

Participants were aged between 18 and 39, and receiving their first, second or third treatment cycle. Half of participants underwent frozen embryo transfer one month after initial egg harvest, whereas the other half received fresh embryo transfer a few days after harvest.

The researchers found that there was no significant difference between the percentage of women who fell pregnant in each treatment group, 27.8 percent for women who froze their embryos compared with 29.6 percent who underwent fresh embryo transfer. In addition, there was no significant difference between the live birth rates, 27.4 and 28.7 percent for frozen and fresh embryo transfer, respectively.

The study also reported a slightly increased risk of preterm birth in the fresh embryo transfer group. However, time to pregnancy was significantly longer in the frozen embryo transfer cohort, leading the authors to conclude that ‘fresh embryo transfer should be used as the gold standard’.

The findings could influence best practice in fertility clinics and are especially relevant given the enormous rise in frozen embryo transfer cycles in recent years – the Human Fertilisation and Embryology Authority’s (HFEAs) latest figures reported a 93 percent increase between 2013 and 2018.

The authors noted that fresh embryo transfer may not be appropriate for all patients, specifically those at a higher risk of the serious side effect of ovarian hyperstimulation syndrome (OHSS). In these patients, frozen embryo transfer can reduce the risk of OHSS.

Dr Stormlund’s team concluded by recommending that: ‘The findings warrant caution in the indiscriminate application of a freeze-all strategy when no apparent risk of ovarian hyperstimulation syndrome is present.’

Source: https://www.bionews.org.uk/page_151306

Endometrioma affects fertility parameters but not embryo quality

Endometrioma affects fertility parameters but not embryo quality

Researchers sought to investigate the effects of endometrioma and the impact of bilaterality on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes.

A Turkish study has found that that presence of endometrioma in patients with endometriosis negatively impacts fertility parameters, but has no effect on embryo quality, clinical pregnancy rates (PR), or live birth rates (LBR).

The study in the Journal of Gynecology Obstetrics and Human Reproduction also concluded bilaterality does not influence any fertility parameters or pregnancy rates.

Done retrospectively, the researchers sought to investigate the effects of endometrioma and the impact of bilaterality on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes.

A total of 159 women who underwent IVF/CSI cycles at Zekai Tahir Burak Women’s Health Education and Research Hospital in Ankara, Turkey, between March 2015 and March 2018, were recruited for the study.

Patients were divided into two groups: the study group (n = 73) of infertile women with either unilateral or bilateral ovarian endometrioma with any IVF indication; and the control group (n = 86) without endometrioma.

Basal follicle-stimulating hormone (FSH) levels and total gonadotropin doses used during ovarian stimulation were significantly higher and antral follicle count (AFC) was significantly lower in the study group compared to the control group.

But the differences in these variables between the unilateral (n = 43) and the bilateral (n = 30) endometrioma group were non-significant.

Anti-Müllerian hormone (AMH) levels for unilateral and bilateral endometrioma were also comparable: 1.4 ng/ML and 1.23 ng/mL, respectively.

However, the number of endometriomas > 4 cm was significantly higher in the bilateral than in the unilateral group.

The study also found that the number of dominant follicles at trigger day and total oocyte retrieved were significantly higher in the control group than in the study group. But when compared between the unilateral and the bilateral endometrioma group, these differences were insignificant.

Still, the number of metaphase II (MII) oocytes was significantly higher in the control group compared to the unilateral group, whereas the difference was non-significant between the control group and the bilateral group.

For all procedures, sperm was obtained via ejaculation, and there were no cycles cancelled in the control group. However, in the study group, 12 cycles were cancelled because fertilized embryos could not be procured: 6 cycles each from the unilateral and bilateral group.

There were also four patients in the study group with no dominant follicle development, two each from the unilateral and bilateral group.

In addition, there were eight total fertilization failures, four each from the two groups.

Given the higher cancelling rates, the prognosis for patients with endometrioma seems to be worse than in patients without endometrioma,” wrote the authors.

On the other hand, the number of embryos achieved and blastocysts obtained were similar between the three groups (no laterality, unilateral and bilateral), as were rates of pregnancy, live birth, and early pregnancy loss.

There was also no statistically significant difference between the control and the unilateral groups for all grades of embryo.

However, the number of grade 2 embryos was significantly lower in the bilateral group compared to the control group. But for blastocyst and grade 1 embryo numbers, the bilateral group had comparable findings to the other two groups.

Based on our results, we speculate that bilaterality doesn’t exert additional damage on ovarian reserve more than unilateral endometrioma does,” wrote the authors.

Read more: https://www.sciencedirect.com/science/article/abs/pii/S2468784720301835

Response to stimulation in IVF may predict longer term health risks

Response to stimulation in IVF may predict longer term health risks

Low ovarian reserve with few eggs collected associated with a higher risk of chronic disease.

A follow-up study of almost 20,000 young women who had a first cycle of IVF in Denmark between 1995 and 2014 indicates that those who responded poorly to treatment, with few eggs collected, are at a significantly increased risk of later age-related diseases.

The findings, according to investigator Mette Wulf Christensen from Aarhus University in Denmark, suggest an “association with early ovarian ageing and an accelerated ageing process in general.”

The results, she explains, are consistent with what we know so far about early menopause, which has been shown in several studies to be associated with an increased risk of cardiovascular diseases, osteoporosis and mortality.

Identifying women at risk of early menopause may thus allow early preventive health initiatives in terms of a healthy lifestyle,” says Christensen.

This is the first time that the yield of eggs in IVF as a measure of ovarian ageing — and thus as a risk predictor of age-related ill-health and mortality — has been investigated in a large-scale cohort study. The results were presented online by Ms Christensen, a PhD student, at the virtual Annual Meeting of ESHRE.

The study was based on the national registries of Denmark in which each individual has their own identifying number, thus allowing cross-linkage between various registries of health outcomes and treatments.

In this case women below the age of 37 who had a first cycle of IVF or ICSI in Denmark between 1995 and 2014 were divided into one of two groups according to their response to ovarian stimulation: those who had produced five or fewer eggs for collection, defined as “early ovarian ageing“; and those who responded normally with at least eight eggs. The number of eggs harvested was thus used as a marker of ovarian reserve. There were 1,234 women in the former group, and 18,614 in the latter.

During the six-year average period of follow-up, the incidence of chronic disease in the two groups was analysed from the cross-linked registry data, providing a real-life estimate of risk for cardiovascular disease, osteoporosis, type-2 diabetes, cancer, and all-cause mortality.

Results showed that women in the early ovarian ageing group had an increased overall risk (by 26%) of all-cause disease when compared to those with a normal ovarian response. This higher risk was statistically significant, and evident in cardiovascular diseases (39% higher) and osteoporosis (more than double).

The two groups were also cross-checked with the “early retirement benefit” register, in which the early ovarian ageing group were also more likely to be listed.

The risk of cancer, other age-related diseases and all-cause death was not significantly different.

Commenting on the implications of the results, Ms Christensen said that, although the common biological mechanisms behind ovarian and general ageing are “somewhat obscure,” the data from this study demonstrate that young women with early ovarian ageing — defined as low oocyte output after FSH stimulation — have an increased risk of age-related morbidity and possibly mortality, “and strongly support the hypothesis that low ovarian reserve may be a useful marker of later health problems.”

Counseling this group of patients at fertility clinics, she added, “may, therefore, be important for introducing preventive measures such as lifestyle changes or the use of HRT to reduce the adverse health risks which follow an earlier menopause.”

Source: European Society of Human Reproduction and Embryology.

Fresh donor eggs appear to be better for IVF than frozen

Fresh donor eggs appear to be better for IVF than frozen

Donor eggs provide the best chance of success for many women undergoing IVF. But it wasn’t clear whether using fresh or frozen donor eggs in IVF improves the chances of success, so a team from the University of Colorado and Duke University analyzed nearly 37,000 IVF cycles using donor eggs over three years.

According to the largest comparison of donor egg IVF cycles to date, using fresh donated eggs for IVF leads to slightly better birth outcomes than frozen.

Data from nearly 37,000 IVF cycles in the US between 2012 and 2015 showed that fresh eggs resulted in a slightly greater chance of a good birth outcome, which the researchers defined as a single, non-premature baby delivered at a healthy birth weight.

‘Our study found that the odds of a good birth outcome were less with frozen than with fresh, but it was a small difference’, says lead author Dr Jennifer Eaton, of Duke Fertility Centre in North Carolina.

When the quality of fertilised eggs and the age of both mother and donor were taken into account, the team found that fresh eggs led to good birth outcomes in 24 percent of cycles compared to 22 percent of the cycles with frozen eggs.

Fresh eggs had a much higher likelihood of implantation and birth than frozen eggs, the study found. Compared to frozen eggs, fresh eggs were associated with almost 25% better chance of live birth and a 10% higher odds for good outcomes.

The rates of embryo implantation, pregnancy and live birth were all significantly higher among the women using fresh eggs compared to frozen, but fresh eggs also led to a 37 percent higher chance of multiple births, which could pose greater risk for both mothers and babies.

Donor eggs are often used for older women or women who have a decreased egg supply. This has led to an increased demand for frozen donor eggs which are a cheaper and faster option than fresh donor eggs. But it was previously unknown which type provides the best birth outcomes.

Although this study is the first to show an advantage of fresh donor eggs over frozen, the researchers say that doctors should take the other benefits of using frozen eggs into account when discussing the best option with patients.

‘Given that frozen eggs have many benefits such as ease, cost, and speed, the decision to use fresh or frozen donor eggs should be made on an individual basis after consultation with a physician’, said Dr Eaton.

In Greece, we do not have egg banks. Therefore, the fresh donor eggs are fertilised by the husband’s sperm. We then proceed to either fresh embryo transfer if the recipient is synchronised with the donor. Otherwise, we perform embryo transfer after thawing the frozen embryos in the future, once the recipient is ready. Success rates are similar in both cases.

The study was published in the journal Obstetrics and Gynaecology: https://journals.lww.com/greenjournal/Abstract/2020/03000/Prevalence_of_a_Good_Perinatal_Outcome_With.27.aspx

Underweight women with endometriosis at higher risk of preterm birth after IVF

Underweight women with endometriosis at higher risk of preterm birth after IVF

Endometriotic patients who were underweight before conception had a significantly higher rate of preterm birth (PTB) than underweight women without endometriosis, according to the findings of a new study publised in Reproductive BioMedicine Online.

Researchers examined the impact of preconception maternal body mass index (BMI) on neonatal outcomes in women with endometriosis who used in vitro fertilization (IVF). They did not find such a difference with other BMI categories.

The retrospective research, performed in China, included of 7,086 women who delivered a singleton live birth via IVF between December 2006 and December 2017 at the Department of Assisted Reproduction of Shanghai Ninth People’s Hospital, which is affiliated with Shanghai Jiao Tong University School of Medicine.

Of the cohort, 1,111 women were diagnosed with endometriosis by laparoscopy or laparotomy, with 45% having ovarian disease and 55% having pelvic endometriosis. The indication for IVF in 74% of the endometriosis group was endometriosis, with the remaining 26% of patients having concomitant male factor infertility.

In the control group of 5,975 women without endometriosis, the indication for IVF was tubal factor infertility in 77% of patients and male factor infertility in the remaining 23% of cases.

Women in both groups were assigned to one of three predefined BMI groups: underweight (< 18.5 kg/m2); normal weight (18.5 to 24.9 kg/m2); or overweight/obese (≥ 25 kg/m2).

All comparisons were between women undergoing cryopreserved embryo transfer, with all embryos transferred into a more natural uterine environment than would have occurred with fresh transfers after ovarian stimulation. This allowed for the precise role of endometriosis to be determined in subsequent neonatal outcomes.

Following stratification by BMI, underweight women with endometriosis had higher rates of PTB (delivery before 37 gestational weeks) than underweight controls: 14.61% versus 3.28%; P < 0.001. However, normal weight and overweight/obese endometriotic women had PTB rates comparable to normal weight and overweight/obese controls.

One possible explanation as to why endometriosis results in higher PTB rates only in the underweight group is the difference in leptin concentration.Leptin, a product of adipose tissue and responsible for regulating lipid metabolism, can reduce body mass by inhibiting food intake and stimulating energy expenditure,” wrote primary author Yun Wang, PhD, and her colleagues from Shanghai Ninth People’s Hospital.

Leptin signaling can also affect the formation of endometriosis though different pathways and is linked with inflammation in endometriosis.

As is well known, inflammation has been implicated in the mechanisms responsible for term and preterm parturition,” the authors wrote.

Genetics is the other mechanism by which a low BMI impacts incidence of PTB. In addition, the genetic factors affecting BMI might be connected to the pathological process of endometriosis, which could result in preterm delivery.

Another finding of the study was a significant interaction between endometriosis and maternal BMI and PTB (P for interaction < 0.05). However, after accounting for potential confounding factors, the PTB rate remained consistently higher in the low BMI subgroup of women with endometriosis: adjusted odds ratio (aOR) = 4.66; 95% confidence interval (CI): 2.54 to 8.57.

Furthermore, the study detected no differences in the rate of early PTB, low birthweight, macrosomia, small for gestational age and large for gestational age between women with endometriosis and controls for any preconception category of BMI.

Overall, the findings underscore the importance of maintaining normal weight in women with endometriosis.

Read more: https://pubmed.ncbi.nlm.nih.gov/32171707/

Source: https://www.contemporaryobgyn.net/endometriosis/maternal-bmi-and-neonatal-outcomes-endometriotic-women-undergoing-ivf

High-resolution 4D imaging of sperm cells moving at top speed could improve IVF treatments

High-resolution 4D imaging of sperm cells moving at top speed could improve IVF treatments

Tel Aviv University (TAU) researchers have developed a safe and accurate 4D imaging method to identify sperm cells moving at a high speed.

The new technology could provide doctors with the ability to select the highest-quality sperm for injection into an egg during IVF treatment, potentially increasing a woman’s chance of becoming pregnant and giving birth to a healthy baby.

“The most common type of IVF today is intra-cytoplasmic sperm injection (ICSI), which involves sperm selection by a clinical embryologist and injection into the woman’s egg. To that end, an effort is made to select the sperm cell that is most likely to create a healthy embryo.”, said the head researcher Prof. Shaked.

Under natural fertilization in the woman’s body, the fastest sperm to reach an egg is supposed to bear high-quality genetic material. Progressive movement allows this “best” sperm to overcome the veritable obstacle course of a woman’s reproductive system.

“But this ‘natural selection’ is not available to the embryologist, who selects a sperm and injects it into the egg,” Prof. Shaked says.

“Sperm cells not only move fast, but they are also mostly transparent under regular light microscopy, and cell staining is not allowed in human IVF. Existing imaging technology that can examine the quality of the sperm’s genetic material may cause embryonic damage, so that too is prohibited. In the absence of more precise criteria, sperm cells are selected primarily according to external characteristics and their motility while swimming in water in a dish, which is very different from the natural environment of a woman’s body”.

“In our study, we sought to develop an entirely new type of imaging technology that would provide as much information as possible about individual sperm cells, does not require cell staining to enhance contrast, and has the potential for enabling the selection of optimal sperm in fertilization treatments.”

The researchers chose light computed tomography (CT) technology for the unique task of sperm cell imaging.

“In a standard medical CT scan, the device rotates around the subject and sends out X-rays that produce multiple projections, ultimately creating a 3D image of the body,” says Prof. Shaked. “In the case of the sperm, instead of rotating the device around this tiny subject, we relied on a natural feature of the sperm itself: Its head is constantly rotating during the forward movement. We used weak light (and not X-rays), which does not damage the cell. We recorded a hologram of the sperm cell during ultrafast movement and identified various internal components according to their refractive index. This creates an accurate, highly dynamic 3D map of its contents without using cell staining.”

Using this technique, the researchers obtained a clear and accurate CT image of the sperm at very high resolution in four dimensions: three dimensions in the space at resolution of less than half a micron (one micron equals one millionth of a meter) and the exact time (motion) dimension of the second sub-millisecond.

“Our new development provides a comprehensive solution to many known problems of sperm imaging,” Prof. Shaked says. “We were able to create high-resolution imaging of the sperm head while it was moving fast, without the need for stains that could harm the embryo. The new technology can greatly improve the selection of sperm cells in vitro, potentially increasing the chance of pregnancy and the birth of a healthy baby.

“To help diagnose male fertility problems, we intend to use our new technique to shed light on the relationship between the 3D movement, structure and contents of sperm and its ability to fertilize an egg and produce a viable pregnancy,” Prof. Shaked concludes. “We believe that such imaging capabilities will contribute to other medical applications, such as developing efficient biomimetic micro-robots to carry drugs within the body.”

Read more: http://www.eng.tau.ac.il/~omni/ScienceAdvances2020.pdf

https://advances.sciencemag.org/content/6/15/eaay7619

What are your chances of having a second IVF baby after fertility treatment for the first?

What are your chances of having a second IVF baby after fertility treatment for the first?

Women have a good chance of having a second child with the help of fertility treatment after the birth of their first child born this way, according to the first study to investigate this, published today in Human Reproduction, one of the world’s leading reproductive medicine journals.

Researchers in Australia calculated that after a woman successfully achieved a live birth using in vitro fertilisation (IVF), also known as assisted reproductive technology (ART), the chances of a second ART baby were between 51% and 88% after six cycles of treatment.

These calculations depended on whether or not previously frozen embryos were used or fresh embryos from a new ovarian stimulation cycle, and on assumptions made about the likely success rate for women who discontinued treatment.

The chances of a second ART baby decreased with increased maternal age.

Compared to women younger than 30 years, the likelihood of women aged 35-39 having a second ART-conceived baby reduced by 22% if they recommenced treatment with a frozen embryo from a previous cycle and by 50% if they recommenced treatment with a new cycle and a fresh embryo.

Factors that improved their chances of a successful second pregnancy included requiring only one cycle and a single embryo transfer to achieve a first live birth, and where infertility was caused by factors affecting the male partner.

Professor Georgina Chambers, director of the National Perinatal Epidemiology and Statistics Unit at the University of New South Wales (Sydney, Australia), looked at data from 35,290 women who received ART treatment between 2009 and 2013 in Australia and New Zealand and had a live baby during this time. These women were followed for a further two years to 2015, providing between two and seven years of follow-up data, and live births up to October 2016 were included.

We calculated two measures: what is a woman’s chance of achieving a second live birth in a particular cycle of treatment if previous cycles have failed, for instance in cycle three if the first two cycles have failed; and what is the overall, or cumulative, chance of a woman achieving a live birth after a particular number of cycles, including all the previous cycles. For example, what is the overall chance of a woman having a baby after up to three cycles,” said Prof Chambers.

A cycle includes the stimulation of the ovaries to mature multiple eggs, the collection of eggs for fertilisation in the laboratory to create embryos, and then all embryo transfer procedures that use the embryos from the egg retrieval procedure. This can include fresh embryo transfers and frozen embryo transfers.

Prof Chambers and her colleagues calculated estimates of cumulative live birth rates (CLBR) for women who were trying for a second ART baby that took account not only of the women who continued treatment, but also those who discontinued treatment.

The conservative CLBR assumed that women who dropped out would have no chance of achieving a second live birth if they had continued treatment. The optimal CLBR assumed these women would have the same chance of a live birth in a particular cycle as women who had continued treatment. The range between the conservative and optimal estimates gives a realistic idea of success rates.

Just over 43% (15,325) of the 35,290 women, with an average (median) age of 36, returned for treatment to conceive a second child by December 2015.

Among these women, 73% used a frozen embryo from the egg retrieval cycle that had resulted in their first child, and for them the CLBR ranged from 61% (conservative estimate) to 88% (optimal estimate) after six cycles. Among the women who had a new stimulation cycle and used a fresh embryo, the CLBR ranged from 51% to 70%.

Overall, 43% of women who recommence treatment with one of the frozen embryos from a previous stimulation cycle will have a baby after their first embryo transfer procedure. Between 61% and 88% of these women will have a baby after six cycles,” said Prof Chambers. “Among those who recommence treatment with a new stimulation cycle and a fresh embryo transfer, 31% will have a baby after their first cycle and between 51% and 70% after six cycles.”

Although success rates declined with female age, the researchers found that after three cycles of treatment, the conservative and optimal CLBRs in women aged 40 to 44 years were 38% and 55% respectively in those that started with a frozen embryo, and 20% and 25% in those recommencing with a new stimulated cycle and fresh embryos.

Read more: https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaa030/5817569

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