Comment:The main news this week is the release of data showing an injection of Kisspeptin can induce ovulation and possibly minimising risk of OHSS. Plus you can now pay to have your chance of pregnancy identified (Univfy IVF Success Program) - amazing. Links to HFEA error report, gender management in Thailand, a new way to think about media for older eggs. Try FertAids Quiz for recent news.
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The "graying" of infertility services: an impending revolution nobody is ready for
"Graying" of the infertility populations in the developed world, a problem with potentially far-reaching medical and societal consequences, has so far been only insufficiently addressed in the literature. As women's postmenopausal life spans already exceed postmenarcheal life spans at the start of the 20th century, the "graying" of infertility services can be expected to further accelerate, no longer as in recent decades bringing only women in th
The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis
Understanding the role of hormones within follicular fluid, as well as how they are altered in disorders which increase ovarian cancer risk, will enhance our ability to assess risk and develop preventative strategies. This review provides an in depth discussion of the logistics of using and studying follicular fluid in ovarian cancer research, and discusses the fluctuations in follicular fluid hormone levels during normal physiological processes
Changes in sex ratio from fertilization to birth in assisted-reproductive-treatment cycles
In-vitro-culture-induced precocious X-chromosome inactivation together with ICSI-induced decrease in number of trophectoderm cells in female blastocysts may account for preferential female mortality at early post-implantation stages and thereby variations in sex ratios at birth in ART cycles.
Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles
Comparison of embryo kinetics in cycles with all embryos implanting (KID+) versus no implantation (KID-) suggested that markers of embryo competence to implant may be different from ability to form a blastocyst. The incidence of multinucleation and reverse cleavage amongst the embryos observed was 25% and 7%, respectively. Over 40% of embryos exhibiting these characteristics did however form blastocysts meeting our criteria for freezing.
A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of ICSI cycles [archive]
The use of reduced oxygen in IVF is reasonable, irrespective of the duration of embryo culture. It improves embryo development and cumulative PR and is also recommended in poor responding cycles.
The effect of two distinct levels of oxygen concentration on embryo development in a sibling oocyte study [Archive]
Conclusions: Implantation, pregnancy and live birth rates are higher, and more good quality embryos are available for transfer and freezing with reduced rather than with atmospheric oxygen concentrations during embryo incubation.
Reduced oxygen tension improves embryo quality but not clinical pregnancy rates: a randomized clinical study into ovum donation cycles
In the ovum donation cycles undergoing day-3 embryo transfers, the use of low O2 tension did not improve ongoing pregnancy rates per cycle and per transfer. However, it benefited embryo quality, demonstrating the potential negative impact of high O2 tension on the in vitro embryo development.
Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged mouse model improves embryo development and viability
This study demonstrates that the addition of DCA to embryo culture media improves mitochondrial output in embryos produced from aged mice. Although DCA itself may be of limited therapeutic value in a clinical setting due to its low threshold of dosage and high toxicity, this proof of concept study does suggest that the addition of a physiological-based mitochondrial stimulator to embryo culture media for aged women may potentially improve IVF out
Adverse incidents in fertility clinics: lessons to learn. 2010 – 2012 [PDF]
More than 60,000 cycles of IVF treatment are carried out each year in the UK. The vast majority of those cycles are carried out without any problem occurring. However, as in any clinical setting, mistakes can happen. As this report shows, the number of incidents which occur each year is relatively low – around 500 (or less than 1% of treatment cycles carried
out). Of those incidents, very few are of the most serious type.
NATA - General Equipment - Calibration and Checks. July 2014 [PDF]
A facility must demonstrate how it has determined which parameters are critical (and non critical) to the overall quality of test and calibration results. As an example, critical parameters may be analytical or quantitative data, or measurements which have a significant contribution to the final result and associated measurement uncertainty.
The CE marking of IVF culture media is a significant development in the field. However, the quality and efficiency of culture media should be monitored closely. Well-designed randomized controlled trials, large epidemiological studies and full transparency should be the next steps. Reliable, standardized models assessing multiple end-points and post-implantation development should replace the mouse embryo assay. Structured long-term follow-up of
Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization
This study demonstrates that a single injection of kisspeptin-54 can induce egg maturation in women with subfertility undergoing in vitro fertilization therapy. Subsequent fertilization of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy.
Twelve babies have been born using a potentially safer way of getting eggs for use in IVF, UK doctors say. The naturally occurring hormone, kisspeptin, was used to stimulate women's ovaries to produce eggs. The pregnancies, reported in the Journal of Clinical Investigation, show the hormone can be used successfully.
Thailand has become a top tourist destination for women seeking gender-selective IVF. The country is one of just three that permit gender selection – the other two are the US and South Africa – and it offers the most affordable procedures.
With no steady source of income, 24-year-old Protima Santra (name changed) finds it difficult to make ends meet. But she has just been able to re-lay the tiles of her leaking roof and send her children for tuition, thanks to the handsome Rs 25,000 that she has recently made. However, she cannot spend the money too lavishly because it has to last the family at least three months after which she will head for the fertility clinic where she had dona
Introducing The Univfy' IVF Success Program and Your Fertility''
The Univfy IVF Success Program is the only online program providing personalized analyses of both in vitro fertilization (IVF) success and IVF cost. IVF is the most effective fertility treatment but can cost $8,000 to $20,000 or more per treatment.
HFEA: More than 1,600 fertility clinic mistakes in three years
Hundreds of adverse events occur in UK fertility clinics each year, according to a report from the Human Fertilisation and Embryology Authority (HFEA). The report shows that 1,679 mistakes were made in UK fertility clinics between 2010 and 2012. This figure adds up to an average of 500 to 600 incidents per year out of the 60,000 IVF cycles conducted annually.
Pregnancy Predictor. - Models to predict the probability of at least ONE live birth. [This link may be from a sponsor]
The model uses information collected from the original egg recovery and from subsequent frozen embryos transfers. The chance of pregnancy is calculated from data where the outcomes of both the fresh and any subsequent frozen embryo transfers are combined and included in you overall chance of having a baby. This is what may be called the CUMULATIVE PREGNANCY RATE.
In this episode, Waljit Dhillo discusses the results from a small clinical trial that evaluated use of the fertility hormone kisspeptin-54 for egg maturation in IVF. Dhillo and colleagues report that kisspeptin-54 treatment resulted in mature eggs that were successfully fertilized and transferred, with pregnancy in 23% of patients.
The increasing pressure on treating older clients is a trend that is showing no signs of fading.
Comment
It seems funny that on one hand IVF is using more complex technology such as time-lapse and PGS to `identify` the good embryos but are increasingly seeing the age of their client base drift towards a group where there are few if any good embryos. The shift towards older clients will see several changes to how IVF is managed. Firstly the overall success rate will fall, more clients will opt of donor eggs (from younger women), there will be more pressure on younger women to either donate or freeze oocytes for future fertility needs, surrogacy and maybe other aspects like mitchondrial transplants. Clinics may need to shift their counselling to suit older clients and may need to partition their reporting to avoid the decrease in outcomes. On the other hand, funding bodies will increasingly look to only support clients with a reasonable chance of success. This will compromise some business models such as in Australia. A good article to read.
Title
A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of ICSI cycles
Summary
There remains some debate about the value of reduced oxygen atmospheres in human IVF but the results from animal models suggest low is better.
Comment
IN this study and a review in EMBRYO CULTURE (methods and protocols), the authors suggest the 5% and 20% have little impact of outcomes for cleavage stage transfers but have an impact on blastocyst transfers and in cycles of poor responders. In other words, healthy oocytes and embryos can survive short term "stress" at 20% O2 but prolonged oxygen stress or if an oocyte/embryo is already struggling, 20% oxygen does not help. Low O2 has never been shown to be detrimental and seems the preferred system.
Title
Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged mouse model improves embryo development and viability
Summary
An interesting study because it has focused on treating age females demonstrating that increasing mitochondrial activity improves outcome
Comment
Almost all of IVF methodology is based upon improving the performance (or really, minimising harm) in mouse and human embryos from young clients. Yet increasingly, more clients do not have youth on their side. This study asks whether embryos from older females (mice) can perform better and shows that they can develop at a higher rate if their mitochondria are stimulated. The authors have pointed out that while the tool they used has little clinical relevance, the viability of embryos from older females can be "rescued". They also have only shown the embryos have more cells, not that they can implant at a higher rate. Maybe this is the start of a set of media that has been developed for older embryos. A long time coming and well overdue. Of course, making embryos from older females implant better is OK but what risks are there in doing so. Still one step at a time.
Title
Adverse incidents in fertility clinics: lessons to learn. 2010 – 2012
Summary
The HFEA has released a report on errors in UK IVF Clinics over the last 3 years. At first glance, it seems a tad worrisome but it all sounds like undue pressure on staff to meet expectations or poor
Comment
The HFEA's report is interesting in that it exists in the public domain and it places a KPI figure of <1% of cycles of any form of incident. There were two important incidents. One where gamete contamination MAY have occurred and the second where there was a breach of confidentiality. Gamete/embryo mix-up is the MAJOR sin and does require constant vigilance and witnessing support from other staff to drive this to zero. There is considerable time pressures on all lab staff but at this one critical time point in treatment, every needs to check and double check. It does not help when increasingly, partners names differ and maybe unfamiliar and difficult to recognise to the staff. Electronic witnessing still has some way to go to be really easy to use but it will ultimately become universal and mandatory. Database developers would do well to integrate this feature into their software. I note that the report mentions that sometimes, the staff need counselling which is understandable. The lab manager needs to continue to check that all staff are following the labs rules (SOP) because if left unattended with the assumption that all staff know what they are doing, staff will wander from the SOP to meet various deadlines. Ultimately, the Lab Manager is a fault for not checking the day to day compliance.
Title
Egg donors cash in on IVF baby boom
Summary
Oh what a interesting world.
Comment
In most western countries where IVF first developed, donation was seen to be altruistic and transparent and non-commercial. But look what's happens in India. There is no comment on whether the Indian egg donation scheme is good or bad but different to Australia or most of Western Europe and the UK. There, donors must donate for only pocket money to pay for "costs" and must be on a register for the children to contact in 20+years and be limited to the number of families able to be created from their total donation. In India, egg donors are paid enough to re-tile one floor, be recruited by agents and sub-agents. It is unclear if the donation is traceable but this is unlikely leading to generations of children unable to track down their biological mother. It would not be surprising if a donor donated to more than one clinic as happened with sperm donation many years ago in Australia. The report indicates hormones are given to recovery ~ 15 eggs, a number that must put some at risk of OHSS even if there is no transfer. The crazy thing is that an Australian (or from elsewhere) can have egg donation in India and return to Australia pregnant and no-one knows (or cares). Seems to make the local rules redundant. Far better to make donation more flexable at home and allow the recipient to choose between an altruistic or a paid donor.
Title
Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization
Summary
A single injection of Kisspeptin-54 is able to induce ovulation in Antagonist managed IVF cycles producing mature oocytes, fertilisation, and pregnancy minimising the risk of OHSS.
Comment
Kisspeptin is the neurological controller of GnRH secretion that has been implicated in control of female reproduction endocrinology apparently being released in different part of the hypothalmus some controlling FSH and other controlling LH release at ovulation. This study used antagonist based COH in a number of IVF clients ceasing the antagonist 24 hours before ovulation induction and using a bolus injection of Kisspeptin-54 to induce a natural LH rise. It seems the degree of ovulation induction was dose dependent and at certain levels was able to trigger oocyte maturation, normal egg recovery, ICSI fertilisation, embryo development and pregnancy. The key is that the Kisspeptin injection used the normal hypothalamic/pituitary axis to induce a 'normal' LH surge but no lingering stimulation often associated with hCG. This means that the risk of OHSS may be significantly reduced. Unlike other alternative triggers for at risk clients such as agonists, Kisspeptin triggers from a higher control level allowing all the pituitary processes to operate normally. The authors expressed caution about many other aspects of IVF including imprinting risks but these will most likely be quickly dismissed to the standard IVF background risk with more cases. An interesting study. Kisspeptin-54 was synthetically manufactured and like all new drugs, time will reveal its safety and efficacy.
IVF Training - Questions relating to mailout links -
Open Challenge and complete Questions
Question
Type
Options
In a prospective sibling oocyte study, 5% O2 showed
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In A Prospective Randomised Study, 5% O2 Showed
2
5
In a randomised oocyte donation programme, low O2 showed:
2
3
KIsspeptin-54 can induce normal ovulation and pregnancy in antagonist managed COH IVF Cycles
1
2
KIsspeptin-54 can induce normal ovulation and pregnancy in antagonist managed COH IVF Cycles
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2
IVFLabOnline - Recent Enteries to IVFLabOnlines product listings.see IVFLabonline
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Vit Kit - Warm NX is an adaptable, cost-effective system for use in the thawing of oocytes, pronuclear zygotes, cleavage stage embryos, and blastocyst stage embryos. Unlike many vitrification kits that feature a mono-buffered system and M199 base med
Vit Kit - Freeze NX is an adaptable, cost-effective system for use in the vitrification of oocytes, pronuclear zygotes, cleavage stage embryos, and blastocyst stage embryos. Vit Kit - Freeze NX is the latest advancement in vitrification media aimed t
S-Cryolock is the slimmer version of the original. It is a versatile, simple and efficient vitrification device that is intended for the holding, cryopreservation and storage of oocytes or embryos in liquid nitrogen.
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