IVF News

Tuesday 27th April, 2021. 3PM EST/ 8PM GMT / 9PM CET

Moderators:

Professor Catherine Racowsky. and Dr. Alison Bartolucci

Speakers:

"Too Hot to Handle: Determining Devitrification Thresholds and Warming Rates of Reproductive Cells"
Dr. Victoria Santos

"FMEA it! A Qualitative and Systematic Tool for Cryogovernance"
Dr. Kristen Ivani

"Clean Dewars and Glass Houses"
Dr. Martine Nijs
This presentation is sponsored by CooperSurgical Fertility Solutions

VIEW HERE

Meenakshi Choudhary MBBS MD PhD FRCOG will present a recently published article on oocyte vitrification in a well-regarded journal with a high impact factor. The presentation will be followed by a live Q&A.

Live birth and perinatal outcomes using cryopreserved oocytes: an analysis of the Human Fertilisation and Embryology Authority database from 2000 to 2016 using three clinical models M Mascarenhas, H Mehlawat, R Kirubakaran, H Bhandari, M Choudhary Hum Reprod. 2020 Dec 13 https://doi.org/10.1093/humrep/deaa34

Note: all participants will get a certificate of participation.

More information and registration on: https://fertility.coopersurgical.com/webinars/live-birth-and-perinatal-outcomes-using-cryopreserved-oocytes/

Researchers have identified a sperm count threshold which optimises the chance of intrauterine insemination (IUI) resulting in pregnancy.

The retrospective study found that while the highest rate of pregnancy per cycle was achieved with a total motile sperm count of over 9 million, pregnancy also occurred using sperm samples with a total sperm motility count of less than 250,000.  

'Since the decline in pregnancy is gradual and continuous, there is no specific threshold above which IUI should be recommended,' the authors said in the study published in the journal Fertility and Sterility. 

IUI is a commonly used fertility treatment for couples experiencing unexplained subfertility. Sperm samples from the male partner are 'washed' in a solution which attracts the most motile sperm cells, and these are then placed directly into the female partner's uterus. The process is less costly and less invasive in comparison to IVF.

Research examining factors which predict the likelihood of a successful pregnancy following IUI therapy have largely focused on female factors such as age or the number of mature ovarian follicle. Studies relating to male sperm count or motility in relation to IUI success have been small in scale with varying results, and until now, there has not been a clear optimum threshold for sperm count following preparation. 

Now, in the largest study to examine the relationship between postwash total motile sperm count and IUI success, researchers have found that a count of over nine million provides the best chance of achieving a pregnancy. 

The retrospective study reviewed the sperm count, from fresh or frozen samples, and subsequent outcome from over 37,000 IUI patients who collectively underwent 92,471 insemination cycles at a single fertility institution between 2002 and 2018. After adjusting for female age, body mass index (BMI) and ovarian stimulation protocol, results showed that the highest rate of pregnancies occurred with a total motile sperm count of over nine million. This count was associated with a pregnancy rate per cycle of 16.7 percent. 

The authors found that the rate of pregnancy 'gradually declined' as the total motile sperm count fell below this threshold. Patients who were aged 35 and above had significantly lower pregnancy rates per cycle. 

However, the study also noted that pregnancies did arise in cases with a total motile sperm count of as low as 250,000, but this was a rare event. Therefore, the authors emphasise that they were not proposing a particular threshold be used but that postwash total motile sperm count may serve a 'unique value' in helping to improve success rates of IUI and guide decisions. They added further research was needed to determine whether other factors influence the outcome of this treatment. 

SOURCES & REFERENCES

Newborns conceived via IVF appear to have lower levels of DNA methylation at certain regions of DNA, when compared to newborns conceived without IVF. 

DNA methylation is a mechanism used by cells to control gene expression which involves the binding of a methyl group to DNA. The addition of methyl groups to DNA switches genes off which in turn inhibits protein production. The addition and removal of methyl groups from DNA occur throughout the lifetime of an individual. Changes in DNA methylation can be induced by any of the treatments used within the IVF procedures including hormone treatment and changes in the culture medium in which the embryos develop. 

'Our study found only small differences in DNA methylation at birth and these were not seen in early childhood. When considered along with our previous studies finding no differences in children's growth and development, our current study should be reassuring to couples who have conceived with fertility treatments and to those considering these methods', said Dr Edwina Yeung, lead author of the research which was conducted at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Maryland. 

The study, published in the journal Fertility and Sterility, examined the differences in DNA methylation at birth and in early childhood (eight to ten years) in children born in New York State from 2008 to 2010. After analysing DNA methylation differences between 157 newborns conceived via IVF and 520 spontaneously conceived newborns, they observed decreased levels of DNA methylation at certain regions of DNA in newborns conceived via IVF. They did not observe any differences in DNA methylation in newborns conceived via intrauterine insemination (IUI) or ovulation induction (OI). These changes were specific to newborns conceived via IVF. 

Follow-up DNA samples were obtained from 152 children between eight to ten years old and analysed for differences in DNA methylation between 23 children conceived via IVF, 34 children conceived via IUI/OI and children conceived without fertility treatment. They reported the lower levels in DNA methylation observed in newborns conceived via IVF did not persist in childhood with the exception of one region, in the GNAS gene located on chromosome 20, which gives rise to a variety of gene products. They also did not observe any differences in DNA methylation in children conceived via IUI or OI.

These findings suggest that further research needs to be carried out to determine how the techniques used in assisted reproduction technologies contribute to methylation differences observed at birth and in childhood. 

This topic was the subject of a recent event by the Progress Educational Trust – see BioNews 1085 for a write up of the event, and 1089 for a film of the event.

SOURCES & REFERENCES

Tuesday 20th April, 2021. 3PM EST/ 8PM GMT / 9PM CET

This session is kindly sponsored by ZyMōt™ Fertility.

Moderators:

Dr. Sarah Martins Da Silva and Dr. Kelly Tilleman

Speakers:

"Sperm Form and Function"
Dr. David Mortimer

"Origins, Evolution, and Clinical Significance of the Tygerberg Strict Criteria"
Dr. Roelof Menkveld

"Training, QC/QA and Decision Limits for Sperm Morphology"
Dr. Lars Bjorndahl
REGISTER

Women experiencing early-stage menopause had their menstrual cycle restored after receiving ovarian injections of platelet-rich plasma (PRP) and gonadotrophins, according to a Taiwanese study, with one woman becoming pregnant after IVF. 

Twelve Han Chinese women were selected to take part in the small pilot study, of whom 11 experienced resumption of their menstrual cycle within an average of 37 days. Mature oocytes were successfully retrieved from six participants using either ovarian stimulation or natural ovulation cycles and fertilised via IVF, with one individual achieving a clinical pregnancy after implantation with a cleavage-stage embryo.

'The retained immature follicles in ovaries of early menopausal women can be enhanced or stimulated to grow to mature follicles employing our new method,' lead author Dr Chao Chin Hsu of Taiwan United Birth-Promoting Experts (TUBE) Fertility Clinic in Tainan, told Healio. 'This administration mode provides another treatment scenario for women of early menopause and those of impending ovarian failure to have better opportunity to conceive using their own eggs.'

Pre-menopausal women often experience higher levels of follicle-stimulating hormone when they are not ovulating, and higher lutenising hormone, than usual. The researchers monitored the levels of these hormones in the participants before and after resumption of menstruation, noting a decline in both cases. 

Dr Jennifer Wu, an obstetrician-gynaecologist at Lenox Hospital, New York, who was not involved in the study warned that the sample size was too small to draw conclusions. 'The percentage success rate for a live birth is not known, and that's what we're really interested in', she told HealthDay.

Additionally, the treatment may only be viable for pre-menopausal women of a certain age. Dr Wu stated that 'Most older patients will have a very hard time getting pregnant, and even if they do get pregnant, they often will have an abnormal pregnancy that doesn't end well'.

However, these findings provide hope for the approximately 12.2 percent of women who experience early menopause, which is defined as menopause before 45 years of age. Due to many women having children later, the impact of this will only increase. 

Future studies should aim to increase and diversify the sample cohort, examining whether similar results can be achieved in women experiencing advanced menopause or by women receiving cancer treatments such as chemotherapy that may cause early menopause. Nonetheless, Dr Stephanie Faubion, medical director of the North American Menopause Society said, the data 'highlights the promise of regenerative medicine in restoring or prolonging fertility.'

The abstract for the study was published in the journal Menopause ahead of publication of the paper.

SOURCES & REFERENCES

The largest study to date into unexplained infertility in men has been conducted by UK and Estonian researchers.

Scientists at the University of Tartu, Estonia, and the Wellcome Sanger Institute, Cambridgeshire, studied the genomes of over 2300 men in Estonia, half of whom had fertility issues. They uncovered a structural variant in the Y chromosome that can predispose men to have little to no sperm production, causing them to be infertile.

Co-author Dr Pille Hallast from the University of Tartu and the Wellcome Sanger Institute said: 'Our study is the largest, most sophisticated look at the genetic variation of this particular Y-chromosomal region that can increase the risk of impaired sperm production in men. By having access to such a large number of patients... we identified a common Y-chromosome subtype that is susceptible to genetic changes leading to low sperm count, but also can go unnoticed and passed down in families until a deletion in this genomic region occurs.'

Infertility is an issue that affects around 10 percent of men in the UK, yet the cause is unknown in approximately 60 percent of cases.

The research, published in the journal e-Life, showed that the presence of the novel genetic variant, discovered on the Y chromosome, increases the risk of infertility in men up to nine-fold. Genetic analysis showed that the variant included an inversion that increases the risk of deletions of portions of DNA that are critical for the development of sperm – known as spermatogenesis.

The study outlines that the inversion itself does not appear to have links to infertility but this structural change predisposes the carrier to instability in this portion of the Y chromosome, increasing the risk of deletions arising spontaneously.

The inversion alone is relatively common in men of European descent and its prevalence in the population suggests inheritance of the subtype goes largely unnoticed until genetic deletions arise that effect sperm production and the carrier experiences fertility issues later in life.

Senior co-author of the study, Dr Chris Tyler-Smith from the Sanger Institute commented on the prevalence of this subtype: 'the biggest surprise is that a Y chromosome subtype with such a deleterious effect on fertility is present in the population at all. Why hasn't it disappeared if it is so harmful? Has it perhaps only started to have this effect on fertility recently, as sperm counts have declined for environmental reasons in the last few decades and resulted in a detrimental combination of genetics and environment?'.

Given that so many cases of low sperm production are still unexplained, this study is particularly significant for future diagnostics. Screening men for this subtype, inversion and deletion would provide a chance for carriers to make informed decisions about family planning.

Professor Maris Laan, senior co-author from the University of Tartu said: 'Being able to identify the genetic reason for these men having impaired sperm production will help give them a diagnosis and access to the support that this brings… While some deletions on the Y chromosome were previously known to interfere with sperm production, understanding at this level of detail is important for the management of male fertility issues, and in this case the options of having children early in life or preserving sperm for later use could be discussed.'

SOURCES & REFERENCES