tag:theconversation.com,2011:/ca-fr/topics/icsi-3036/articlesICSI – La Conversation2021-04-22T22:40:53Ztag:theconversation.com,2011:article/1582272021-04-22T22:40:53Z2021-04-22T22:40:53ZStandard IVF is fine for most people. So why are so many offered an expensive sperm injection they don’t need?<figure><img src="https://images.theconversation.com/files/394939/original/file-20210414-13-10bvrbn.jpg?ixlib=rb-1.1.0&rect=0%2C4%2C1000%2C727&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/intracytoplasmic-sperm-injection-icsi-part-ivf-1394225165">from www.shutterstock.com</a></span></figcaption></figure><p>An expensive IVF technique, routinely offered in fertility clinics around the world, offers no extra benefits to standard IVF in the vast majority of cases, our new research shows.</p>
<p>The technique, known as intracytoplasmic sperm injection or ICSI, was developed to help couples where the man has a low sperm count. But it is now the main fertilisation method clinics use in Australia and New Zealand, even when sperm counts are normal. </p>
<p>In an article published today in <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00535-3/fulltext">The Lancet</a> we show that when there’s a normal sperm count, ICSI does not improve the chance of a baby when compared with standard IVF. So why do clinics routinely offer it?</p>
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Read more:
<a href="https://theconversation.com/considering-using-ivf-to-have-a-baby-heres-what-you-need-to-know-108910">Considering using IVF to have a baby? Here's what you need to know</a>
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<h2>What is ICSI?</h2>
<p>In IVF, several thousand sperm compete to be the one to fertilise an egg. However, for the small percentage of couples with what doctors call severe male-factor infertility — for instance, where there is a very low sperm count or the sperm doesn’t look or move normally — IVF is not an option. </p>
<p>In 1992, ICSI <a href="https://pubmed.ncbi.nlm.nih.gov/1351601/">was introduced</a>, where a single sperm was injected into the egg using a glass needle. This allowed the expansion of IVF to people where low sperm counts or poor sperm quality was an issue.</p>
<p>Its introduction across the world has helped thousands of couples have biologically related children, who otherwise would have needed donor sperm or remained childless.</p>
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<a href="https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="IVF versus ICSI" src="https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">With IVF, thousands of sperm compete to fertilise an egg. But with ICSI, a single sperm is injected into the egg.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/types-artificial-fertilization-egg-spermotozoydami-plant-1437755195">from www.shutterstock.com</a></span>
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<h2>How common is it?</h2>
<p>ICSI was expected to be used only where male infertility was an issue, but over time it has become the most used method of fertilisation even when it isn’t.</p>
<p>In the United States, between 1996 and 2012, ICSI use <a href="https://jamanetwork.com/journals/jama/fullarticle/2091303">increased</a> from 15% to 67% of couples where the male has a normal sperm count; in Europe about <a href="https://pubmed.ncbi.nlm.nih.gov/30032255/">70% of cycles</a> use ICSI.</p>
<p>In <a href="https://npesu.unsw.edu.au/sites/default/files/npesu/data_collection/Assisted%20Reproductive%20Technology%20in%20Australia%20and%20New%20Zealand%202018_0.pdf">Australia</a> around 60% of cycles used ICSI in 2018. This is even though <a href="https://www.auanet.org/guidelines/azoospermic-male-best-practice-statement">only</a> 30% of infertile couples have male infertility and 15% severe male infertility.</p>
<p>Clinics in Australia use ICSI to different extents. For instance, in Victoria in 2019-20, ICSI was used between <a href="https://www.varta.org.au/sites/default/files/2021-01/varta-annual-report-2020.pdf.pdf">34% and 89%</a> of the time, depending on the clinic.</p>
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Read more:
<a href="https://theconversation.com/sperm-why-these-secretive-swimmers-are-the-key-to-the-future-of-fertility-and-contraception-81773">Sperm: why these secretive swimmers are the key to the future of fertility – and contraception</a>
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<h2>What we did and what we found</h2>
<p>Today we report, with our collaborators in Vietnam, the results of a large study in which more than 1,000 infertile couples with a normal sperm count were randomly allocated to ICSI or IVF. We found couples in either group were just as likely to have a baby.</p>
<p>This adds to evidence from other <a href="https://pubmed.ncbi.nlm.nih.gov/29897449/#:%7E:text=What%20is%20known%20already%3A%20The,with%20non%2Dmale%20factor%20infertility">large observational studies</a> in as many as 15,000 women that the widespread use of the more expensive and technically demanding ICSI does not offer any benefit to couples where the man has a normal sperm count. </p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/32896391/">Excellent clinics</a> internationally and in Australia perform ICSI in fewer than 35% of their treatments, while achieving success rates equal to or better than clinics using ICSI more commonly.</p>
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Read more:
<a href="https://theconversation.com/fertility-miracle-or-fake-news-understanding-which-ivf-add-ons-really-work-118585">Fertility miracle or fake news? Understanding which IVF 'add-ons' really work</a>
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<h2>How did ICSI become so popular?</h2>
<p>There are a <a href="https://www.hfea.gov.uk/treatments/treatment-add-ons/">growing number</a> of fertility treatments that <a href="https://www.fertstert.org/article/S0015-0282(19)32454-9/fulltext">aren’t backed by reasonable evidence</a>. </p>
<p>Some are relatively cheap, such as vitamins and antioxidants. Others are invasive or expensive. These include <a href="https://www.hfea.gov.uk/treatments/treatment-add-ons/endometrial-scratching/">endometrial scratching</a> (where the lining of the uterus is scraped with a thin tube, which is said to improve the chance of an embryo implanting), video microscopy of embryos, and <a href="https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/03/preimplantation-genetic-testing">pre-implantation genetic diagnosis</a> for potential chromosome abnormalities (where an embryo is tested for genetic disease before being implanted).</p>
<p>In fact, ICSI is about A$500 more expensive than standard IVF, although costs vary between clinics, and some costs can be claimed on <a href="http://www9.health.gov.au/mbs/fullDisplay.cfm?type=item&q=13218&qt=item">Medicare</a> under specific circumstances.</p>
<p>So why are these so-called “add-ons” or “adjuvants” so common?</p>
<p>Fertility treatment, especially IVF and ICSI, is overwhelmingly practised in the private sector in Australia and New Zealand. It is strongly marketed to the public and promoted in social media by individual doctors, clinics and corporations. Doctors and clinics also compete for patients, often offering <a href="https://theconversation.com/fertility-miracle-or-fake-news-understanding-which-ivf-add-ons-really-work-118585">unproven therapies</a>.</p>
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Read more:
<a href="https://theconversation.com/the-business-of-ivf-how-human-eggs-went-from-simple-cells-to-a-valuable-commodity-119168">The business of IVF: how human eggs went from simple cells to a valuable commodity</a>
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<p>Couples may overlook a doctor seeking to practise fertility medicine based solely on evidence, and instead find a nearby clinic or doctor <a href="https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/ajo.13321">prepared to offer</a> add-ons they believe will improve their chance of a baby.</p>
<p>In the case of ICSI, doctors may recommend it for fear of patients’ reactions if the eggs don’t fertilise, even if ICSI doesn’t improve the ultimate chance of a baby for those with a normal sperm count.</p>
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<h2>What can we do about it?</h2>
<p>Infertility is distressing and, in most cases, can be easily treated with good advice, simple drugs and, if needed, quality assisted reproductive procedures such as IVF.</p>
<p>However, unrestrained, unnecessary use of ICSI is a salutary example of why we need to act on widely accepted evidence.</p>
<p>Until now, the fertility industry has promoted <a href="https://www.abc.net.au/radio/programs/pm/ivf-specialists-hit-back-at-four-corners-story-on/7464870">self-regulation</a> over being made to follow government-imposed, evidence-based guidelines of which fertility treatments are needed. And there’s a <a href="https://www.fertstert.org/article/S0015-0282(19)32454-9/fulltext">growing concern</a> the industry is not doing enough to combat unproven and expensive treatments.</p>
<p>Couples with infertility belong to a <a href="https://pubmed.ncbi.nlm.nih.gov/18025030/">very vulnerable group</a> who will do almost anything to achieve a pregnancy. They deserve our dedicated care and evidence-based treatment.</p><img src="https://counter.theconversation.com/content/158227/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robert Norman is not involved financially in any IVF or fertility clinic </span></em></p><p class="fine-print"><em><span>Ben W. Mol receives funding from NHMRC (Investigatorgrant GNT1176437) Guerbet, and Ferring.
</span></em></p>Our new study shows a widely used fertility treatment, known as ICSI, is no better than standard IVF for most people. Yet, it’s being routinely offered around the world.Robert Norman, Professor of Reproductive and Periconceptual Medicine, The Robinson Institute, University of AdelaideBen W. Mol, Professor of Obstetrics and Gynaecology, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1185852019-06-12T04:17:01Z2019-06-12T04:17:01ZFertility miracle or fake news? Understanding which IVF ‘add-ons’ really work<figure><img src="https://images.theconversation.com/files/279040/original/file-20190612-32335-1y20r9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Almost 65% of couples in Australia and New Zealand are using ICSI as part of their IVF treatment.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>In recent years, we’ve seen <a href="https://www.bmj.com/content/364/bmj.l226.full">increasing scrutiny</a> about the procedures being delivered in the IVF clinic, often referred to as “add-on” or supplementary technologies. </p>
<p>These are optional extras you may be offered on top of your normal fertility treatment, often at an additional cost. </p>
<p>Today in the Australian and New Zealand Journal of Obstetrics and Gynaecology (<a href="https://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1111/ajo.13004?author_access_token=jjPq3iXJQomi60Q5hMwOjota6bR2k8jH0KrdpFOxC67xq5rPvp2w69lKb_OpAURPfx67cXBTyghmpwgT2AipVYWX4fiJojh0mPOIoNigg8K4ugFEaqnPcs0jYgW9aiir">ANZJOG</a>), Australian researchers report the use of one very commonly used technology called ICSI (intra-cytoplasmic sperm injection) may be ineffective in certain groups to which it’s offered.</p>
<p>This is concerning because prospective parents using IVF are often vulnerable, and willing to pay <a href="https://www.abc.net.au/news/2019-05-05/fertility-adds-ons-a-waste-a-money-according-to-some-experts/11004434">thousands of dollars</a> for any procedure they believe might improve their chance of conceiving. We need to ensure whatever they’re being offered is grounded in the strongest scientific evidence.</p>
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Read more:
<a href="https://theconversation.com/your-questions-answered-on-donor-conception-and-ivf-45715">Your questions answered on donor conception and IVF</a>
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<h2>What is ICSI?</h2>
<p>ICSI involves injecting a single sperm into an egg to facilitate fertilisation (which would normally happen in the fallopian tube, or in a dish in the process of <em>in vitro</em> fertilisation). </p>
<p>It was originally developed to help couples with male-factor infertility (when a fertility issue is identified with the male, such as poor quality or very low numbers of sperm). </p>
<p>For these couples, where fertilisation may be the barrier to fertility, the barrier is removed by injection of the sperm directly into the egg.</p>
<p>While ICSI may not necessarily be classified as an add-on technology, it’s now used widely in IVF clinics – notably, more widely than just for couples diagnosed with male infertility.</p>
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<img alt="" src="https://images.theconversation.com/files/279038/original/file-20190612-32342-1nxi4a0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279038/original/file-20190612-32342-1nxi4a0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=483&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279038/original/file-20190612-32342-1nxi4a0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=483&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279038/original/file-20190612-32342-1nxi4a0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=483&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279038/original/file-20190612-32342-1nxi4a0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=608&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279038/original/file-20190612-32342-1nxi4a0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=608&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279038/original/file-20190612-32342-1nxi4a0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=608&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">ICSI differs from traditional IVF in that it involves a single sperm being injected directly into an egg.</span>
<span class="attribution"><span class="source">From Shutterstock.com</span></span>
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<p>Data collected from <a href="https://npesu.unsw.edu.au/sites/default/files/npesu/data_collection/Assisted%20Reproductive%20Technology%20in%20Australia%20and%20New%20Zealand%202016.pdf">Australia and New Zealand</a> shows that almost 65% of couples are having ICSI as part of their fertility treatment. These numbers reflect global trends, with some countries such as Italy reporting almost <a href="https://academic.oup.com/humrep/article/29/10/2099/646277">exclusive use of ICSI</a>. </p>
<p>But the level of male infertility in couples with fertility issues is only about <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691969/">40-50%</a>.</p>
<h2>What does this research find?</h2>
<p>Researchers from a Melbourne IVF clinic <a href="https://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1111/ajo.13004?author_access_token=jjPq3iXJQomi60Q5hMwOjota6bR2k8jH0KrdpFOxC67xq5rPvp2w69lKb_OpAURPfx67cXBTyghmpwgT2AipVYWX4fiJojh0mPOIoNigg8K4ugFEaqnPcs0jYgW9aiir">looked at historical data</a> collected between 2009 and 2015. </p>
<p>In reviewing more than 3,500 cycles of fertility treatment, they examined couples who had exclusively female-factor infertility (the female has an identified cause of fertility), or unexplained infertility, and excluded couples who had male-factor infertility. </p>
<p>They went on to compare the success rates of both <em>in vitro</em> fertilisation (natural fertilisation in a dish), and ICSI (sperm injection directly into the egg). They wanted to understand whether ICSI was beneficial to more couples than just those with male-factor infertility, given the widespread use of the technology around the world.</p>
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Read more:
<a href="https://theconversation.com/five-traps-to-be-aware-of-when-reading-success-rates-on-ivf-clinic-websites-68806">Five traps to be aware of when reading success rates on IVF clinic websites</a>
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<p>They found couples who had standard <em>in vitro</em> fertilisation were more likely to to take home a baby than couples who had ICSI, suggesting the technology may actually be hindering a couple’s chance of starting a family. </p>
<p>They report that for every 15 couples who have the ICSI procedure when the couple do not have diagnosed male-factor infertility, one less pregnancy is achieved.</p>
<h2>What can’t we assume from the paper?</h2>
<p>When scientists perform retrospective analyses (those done on historical data which is already collected), there are a number of things which are impossible to extract and understand (limitations). </p>
<p>While the paper reports that couples won’t benefit from ICSI if they don’t have a male-factor infertility diagnosis, unpicking all of the factors that may have led to that outcome is very difficult.</p>
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<img alt="" src="https://images.theconversation.com/files/279039/original/file-20190612-32361-1n50kx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279039/original/file-20190612-32361-1n50kx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279039/original/file-20190612-32361-1n50kx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279039/original/file-20190612-32361-1n50kx9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279039/original/file-20190612-32361-1n50kx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279039/original/file-20190612-32361-1n50kx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279039/original/file-20190612-32361-1n50kx9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">For couples using IVF, making sense of the many ‘add-on’ procedures available can be confusing.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
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<p>For example, we don’t know if a clinician was encouraging the use of ICSI in couples who appeared to be more infertile, meaning this group were less likely to conceive regardless of the intervention. </p>
<h2>We need more evidence</h2>
<p>Given ICSI is an additional cost to couples seeking fertility care (hundreds of dollars on top of <em>in vitro</em> fertilisation), this study supports the need for further exploration of the benefits (or lack thereof) of technology in the fertility sector. </p>
<p>The highest quality of evidence comes from randomised controlled trials, where data is collected prospectively, once a research question and hypothesis have been determined, and with strict criteria for patient inclusion and treatment. </p>
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Read more:
<a href="https://theconversation.com/considering-using-ivf-to-have-a-baby-heres-what-you-need-to-know-108910">Considering using IVF to have a baby? Here's what you need to know</a>
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<p>Randomised controlled trials would be the ultimate way to determine whether ICSI – and many of the add-on technologies in the IVF arena such as time-lapse imaging, embryo glue, and assisted hatching – will improve a couple’s chances of taking home a healthy baby. </p>
<p>Many of the technologies currently used for fertility treatment lack this high-level empirical evidence.</p>
<h2>Asking the right questions</h2>
<p>ICSI is still a suitable treatment for many fertility patients, and your doctor can explain why the procedure is right for you and your infertility diagnosis – particularly if you have confirmed male-factor infertility.</p>
<p>When discussing your treatment with your fertility specialist, you should ask them if all the technologies they are suggesting are supported by the highest quality scientific evidence.</p>
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Read more:
<a href="https://theconversation.com/health-check-when-does-fertility-decline-21383">Health Check: when does fertility decline? </a>
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<p>If you have learned about add-on technologies in your own searches, you should ask your doctor to explain the current state of evidence with that particular technology, for a patient in your situation (age, fertility status, and so on). There is also useful advice to be found <a href="https://www.varta.org.au/resources/blogs/what-you-need-know-about-ivf-add-ons">online</a>.</p>
<p>Researchers and doctors still don’t have all the answers when it comes to IVF add-ons. But asking these questions may save you from unnecessary costs and procedures.</p><img src="https://counter.theconversation.com/content/118585/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hannah Brown does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>It can be difficult to understand all the ‘add-on’ procedures available with IVF. A new study finds one popular fertility technology, ICSI, is being offered to couples it might not be suitable for.Hannah Brown, Postdoctoral Research Affiliate, University of Adelaide; Chief Science Storyteller, South Australian Health & Medical Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1138172019-03-21T18:04:02Z2019-03-21T18:04:02ZA new procedure may preserve fertility in kids with cancer after chemo or radiation<figure><img src="https://images.theconversation.com/files/265022/original/file-20190321-93028-tlxss5.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C788%2C592&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A 12-week-old baby female macaque, named Grady, was born from frozen testicular tissue. </span> <span class="attribution"><span class="source">Oregon Health and Science University</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Cancer in children was often a death sentence in decades past, but new therapies are saving lives. Many of these treatments such as chemotherapy and radiation, however, make children infertile. Now, new research is showing one strategy to preserve their fertility so that someday they can have their own biological children.</p>
<p>Many childhood cancer survivors have remained beyond the reach of current assisted reproductive technologies because they are not able to produce mature sperm or eggs. Adult patients have the option to freeze eggs or sperm before treatment and use those samples in the future to achieve pregnancy using assisted reproductive technologies. Unfortunately, those options are not available to children who are not yet able to produce mature eggs or sperm.</p>
<p>Now <a href="http://orwiglab.org.s104505.gridserver.com/lab-members/kyle-orwig/">I</a> and my colleagues in <a href="http://orwiglab.org">the Orwig lab</a> at the Magee-Womens Research Institute of the University of Pittsburgh Medical Cancer have developed a next-generation reproductive technology by figuring out <a href="http://science.sciencemag.org/cgi/doi/10.1126/science.aav2914">how to preserve fertility in pediatric cancer patients</a> who might face infertility after chemotherapy or radiation.</p>
<h2>Pediatric cancer therapies</h2>
<p>About <a href="https://curesearch.org/Childhood-Cancer-Statistics">40,000 kids undergo cancer treatments</a> each year, and 80 percent of children will survive and can look forward to a full and productive life. The bad news is that treatment comes at a cost: About 30 percent of adult survivors of these childhood cancers discover that their lifesaving cancer treatment had an unintended side effect – infertility. Cancer survivors report that fertility is important to them, and while adoption or other family building options are available, those options are not always accessible or desired. </p>
<p>In our current study, we used a juvenile male macaque to test whether it was possible to collect and then freeze immature testicular tissues – which produce mature sperm only after puberty. </p>
<p>We began our experiment by surgically removing this tissue from macaques, which we immediately froze. As the animals neared puberty, the testicular tissue was thawed and grafted just under the skin of the same monkey’s back or scrotum. </p>
<p>The grafts matured during the next several months under the influence of pubertal hormones from the brain. The grafts grew and produced testosterone, which is required for sperm production. We retrieved the testicular tissues eight to 12 months after the grafting procedure, dissected it and discovered that all of the grafted tissue produced mature sperm. </p>
<p>My team then collected this sperm and sent it to our collaborators in the <a href="https://www.ohsu.edu/xd/research/centers-institutes/onprc/research-services/research-support/art-esc.cfm">Assisted Reproductive Technology Core of the Oregon National Primate Research Center</a> at the Oregon Health and Science University, who injected it into an egg from a female macaque – a procedure called <a href="https://www.cdc.gov/art/key-findings/icsi.html">intracytoplasmic sperm injection</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/265043/original/file-20190321-93044-1o3ckd9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/265043/original/file-20190321-93044-1o3ckd9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=278&fit=crop&dpr=1 600w, https://images.theconversation.com/files/265043/original/file-20190321-93044-1o3ckd9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=278&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/265043/original/file-20190321-93044-1o3ckd9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=278&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/265043/original/file-20190321-93044-1o3ckd9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=349&fit=crop&dpr=1 754w, https://images.theconversation.com/files/265043/original/file-20190321-93044-1o3ckd9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=349&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/265043/original/file-20190321-93044-1o3ckd9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=349&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In the intracytoplasmic sperm injection process, a single sperm is injected directly into an egg. This is how the team at the Oregon Health Sciences University created Grady.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendering-icsi-intracytoplasmic-sperm-injection-745613476">medistock/Shutterstock.com</a></span>
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<p>We then checked the eggs to see which ones were successfully fertilized by the sperm. Eleven of the resulting embryos were transferred into six surrogate female macaques, resulting in one pregnancy that produced a healthy baby girl that we named Grady, which stands for graft-derived baby. </p>
<p>This is the first study to prove that sperm from frozen and thawed primate testicular tissue grafts were able to fertilize eggs and produce a healthy baby. </p>
<h2>Implications for the human fertility clinic</h2>
<p>The freezing and thawing aspect is important because a prepubertal cancer patient may need to keep their testicular or ovarian tissue in frozen storage for years or even decades before they need them for reproductive purposes. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=874&fit=crop&dpr=1 600w, https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=874&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=874&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1098&fit=crop&dpr=1 754w, https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1098&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/265040/original/file-20190321-93032-uh3ayv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1098&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Grady, here at 11 months, was born from frozen testicular tissue.</span>
<span class="attribution"><span class="source">Oregon Health and Science University</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Combined with nearly two decades of work by other researchers in <a href="http://doi.org/10.1038/nature00918">mice</a>, <a href="https://doi.org/10.1371/journal.pone.0070989">pig</a> and <a href="http://doi.org/10.1095/biolreprod.103.025536">monkey</a> models, we believe that <a href="http://science.sciencemag.org/cgi/doi/10.1126/science.aav2914">our results provide important preclinical safety and feasibility</a> data to justify translating this technique to the human fertility clinic in the next two to five years. </p>
<p>I believe we owe this to our patients who have already accepted the risk of testicular biopsy surgery and trusted us to develop next-generation reproductive therapies.</p>
<p>Academic centers around the world, including the <a href="https://mageewomens.org/research/research-centers/fertility-preservation-program/">Fertility Preservation Program of UPMC</a>, are freezing testicular tissues for boys and ovarian tissues for girls in anticipation that those tissues can be matured in the future to produce sperm or eggs and biological offspring. </p>
<p>There is one documented case of an adult survivor of a childhood cancer who had a <a href="http://doi.org/10.1093/humrep/dev128">baby after her frozen ovarian tissues were transplanted</a> back into her body. There are no documented births from frozen testicular tissues. Our group has been <a href="https://fertilitypreservationpittsburgh.org/">freezing testicular tissue for boys and ovarian tissues for girls</a> since 2011 and has preserved tissues for nearly 250 patients (206 testicular tissues and 41 ovarian tissues). </p>
<p>Therefore, <a href="http://orwiglab.org/">our laboratory</a> is committed to responsibly developing the next generation of assisted reproductive technologies that will allow our patients to use their tissues to achieve their reproductive goals. </p>
<p>All patients should be informed about the reproductive side effects of their medical treatments and about <a href="https://fertilitypreservationpittsburgh.org/">options to preserve their fertility</a> immediately at the time of diagnosis. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/C_F5awyrums?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Kyle Orwig describes how this team harvested tissue, froze and thawed it, and used it to produce mature sperm that successfully fertilized an egg.</span></figcaption>
</figure><img src="https://counter.theconversation.com/content/113817/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kyle Orwig receives funding from the Eunice Kennedy Shriver National Institute for Child Health and Human Development.</span></em></p>Children with cancer not only endure chemotherapy or radiation treatment but they may also face infertility in adulthood. Now a new procedure, just proven in monkeys, may be close to use in humans.Kyle Orwig, Professor of OB/GYN and Reproductive Sciences, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1069512018-11-16T14:09:11Z2018-11-16T14:09:11ZWhat is the ‘right’ age to have a child?<figure><img src="https://images.theconversation.com/files/245935/original/file-20181116-194488-19it793.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/128671076?src=JlMkvanhZBco-takW5inrw-1-12&size=medium_jpg">Malakhova Ganna/Shutterstock</a></span></figcaption></figure><p>Over the past three decades, there has been a steady increase in the average age of parents. Advances in fertility science mean that people can, literally, put their eggs or sperm on ice and delay the start of parenthood. Many large companies, such as Apple, Facebook and Google, now <a href="http://uk.businessinsider.com/egg-freezing-at-facebook-apple-google-hot-new-perk-2017-9">offer egg freezing</a> to employees as part of their healthcare package. Putting off having a baby has never been easier or more socially acceptable. But is it a good thing?</p>
<p>There are three things to consider. Will your child be healthy? Will you get pregnant? How much will it cost?</p>
<p>Parents have a <a href="https://www.ncbi.nlm.nih.gov/pubmed/12058767">moral obligation</a> to give their child the best start in life. But children born to <a href="https://www.ncbi.nlm.nih.gov/pubmed/15863534">mothers</a> over the age of 35 and <a href="https://www.nature.com/articles/tp2016294">fathers</a> over the age of 45 are at greater risk of having genetic and neurodevelopmental disorders, such as schizophrenia and autism, which arguably affects the child’s quality of life.</p>
<p>Also, older parents are more likely to need assisted reproduction, such as IVF, which is associated with babies being born early or with low birth weight. Babies born via IVF are also at higher risk of <a href="https://doi.org/10.1093/humupd/dms062">cardiovascular and metabolic disease</a> in later life. </p>
<p>If prospective parents freeze their eggs or sperm when they are younger, they can reduce some age-associated risks but not those due to IVF. The method of fertilisation in IVF with frozen eggs is intracytoplasmic sperm injection (ICSI), where sperm is injected into the egg. ICSI can also <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1008095">increase the risk</a> of birth defects in children. Using ICSI is also more common in older men where <a href="https://doi.org/10.1016/j.arr.2014.10.007">sperm motility is poor</a>. Again, not the best start in life.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/tick-tock-for-healthy-mums-and-kids-dads-age-counts-105962">Tick-tock – for healthy mums and kids, dad’s age counts</a>
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</em>
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<h2>So you’ve decided to wait</h2>
<p>If you want to wait to have children, you are not alone. </p>
<p>Most couples will fall pregnant after trying for a year. Although <a href="https://www.nhs.uk/conditions/infertility/">one in seven</a> couples has trouble conceiving – and age is a big player in this. <a href="https://www.ncbi.nlm.nih.gov/pubmed/14704244">One in six women</a> aged between 35 and 39 years of age will not conceive after one year. If their partner is over 40, this drops to more than one in four. </p>
<p>IVF is seen by many as a fail-safe way of conceiving, but its success is also governed by age. For a woman using her own eggs, the success of IVF over 40 is <a href="https://www.hfea.gov.uk/treatments/explore-all-treatments/in-vitro-fertilisation-ivf/">less than 10%</a>. </p>
<p>The risks of delaying parenthood have been simulated with <a href="https://doi.org/10.1093/humrep/deh304">computer modelling</a>. If a 30-year-old woman delays trying for a baby from age 30 until 35, her chances of falling pregnant are reduced by 9%, but IVF will only compensate for 4%. </p>
<p>And if you want to freeze eggs, great. Except women produce fewer eggs (“oocytes”) as they get older, so older women may need more rounds of stimulation to store the <a href="https://www.ncbi.nlm.nih.gov/pubmed/27031375">eight to ten eggs</a> needed for a reasonable chance of a successful birth – and this can be extremely expensive. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/hard-evidence-does-fertility-really-drop-off-a-cliff-at-35-29113">Hard Evidence: does fertility really 'drop off a cliff' at 35?</a>
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</em>
</p>
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<h2>What will it cost you?</h2>
<p>Although IVF is expensive, there are also other significant indirect costs of having a child. </p>
<p>The “motherhood wage penalty” is often cited in economic discussions about the effect of motherhood on women’s careers. It is the loss of earnings women are subjected to as they move into a non-paid job for a period of time. There is some evidence to suggest that women can <a href="https://doi.org/10.1007/s00148-009-0296-x">earn more</a> by delaying motherhood from their early twenties to early thirties.</p>
<p>But this wage penalty does not appear to be gender specific. A paternity quota of parental leave was introduced by the Norwegian government in 1993, and a study found a similar <a href="https://link.springer.com/article/10.1007/s13524-013-0233-1">negative effect on the earnings of stay-at-home fathers</a>.</p>
<p>The bottom line is, if you take time out to have a family there will be a drop in earnings.</p>
<h2>When to start?</h2>
<p>The scientific data is clear. The “right” age to have a child according to your biological clock is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1215541/">under 35 for women</a> and under 40 for men. </p>
<p>More than <a href="https://doi.org/10.1080/14647273.2018.1482569">75% of young people underestimate</a> the impact of age on male and female fertility – yet only <a href="https://doi.org/10.1007/s10815-018-1273-7">27%</a> of doctors discuss this with patients aged 18-34 years who wish to delay childbearing for social reasons. There needs to be a greater awareness about the risks of delaying family planning, and family doctors should play a more proactive role in this.</p>
<p>So, ultimately, if you want to have a child, the right age may be sooner than you thought.</p><img src="https://counter.theconversation.com/content/106951/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charlotte Walker receives funding from the Clarendon Fund for her DPhil.
</span></em></p><p class="fine-print"><em><span>Suzannah Williams received funding from MRC. </span></em></p>There are many things to consider when choosing when to have a child.Charlotte Walker, DPhil Candidate in Women's and Reproductive Health, University of OxfordSuzannah Williams, Principal Investigator, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/678472017-01-15T19:02:15Z2017-01-15T19:02:15ZWhat’s the point of sex? It’s communication at a biological level<figure><img src="https://images.theconversation.com/files/150642/original/image-20161219-26097-gc4mgx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Sex is a form of biological communication, and women use it to make decisions on whether to invest in a pregnancy. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/532126837?src=pQ1kr9N-uQLD_ez8OB_3gw-5-84&id=532126837&size=huge_jpg">from www.shutterstock.com </a></span></figcaption></figure><p><em>The act of penetrative sex has evolved over millions of years as a mechanism to deliver sperm to eggs and initiate pregnancy. But there’s more to sex than just the meeting of two sets of genes. The ‘What’s the point of sex?’ series examines biological, physical and social aspects of sex and gender.</em></p>
<p><em>Today’s piece looks at how a woman’s immune system responds to sexual intercourse and facilitates healthy pregnancy.</em> </p>
<hr>
<p>Most people think just one sperm is needed to fertilise a woman’s egg and make a healthy pregnancy. This underpins a common view that all the other sperm – and all the other sex – are surplus to requirements, at least when it comes to conceiving a pregnancy. </p>
<p>However, biologists now believe sexual intercourse is not just a sperm delivery process, but also a kind of biological communication. Regardless of whether fertilisation occurs, sperm and other components of the ejaculated fluid trigger subtle changes in the immune system of women. </p>
<p>This has consequences for pregnancy should it happen later. More broadly, the importance of regular sexual activity also has implications for fertility planning, and for IVF and other forms of assisted reproduction, which generally do not take sexual practice or history into account. </p>
<h2>Sperm swim in a soup of molecular messages</h2>
<p>Evidence from <a href="https://www.ncbi.nlm.nih.gov/pubmed/26178848">animal research</a> and <a href="https://www.ncbi.nlm.nih.gov/pubmed/27485480">clinical studies</a> has led researchers to conclude seminal fluid – the fluid sperm are bathed in following ejaculation – plays an important role in fertility. </p>
<p>Seminal fluid <a href="https://www.ncbi.nlm.nih.gov/pubmed/27485480">contains small molecules</a> that act as biological signals. Once deposited in the vagina and the cervix of a woman, these <a href="https://www.ncbi.nlm.nih.gov/pubmed/23480148">persuade the woman’s immune system</a> to adopt a profile that tolerates (that is, recognises and accepts) sperm proteins known as “transplantation antigens”. </p>
<p>The tolerant profile matters if fertilisation takes place. Immune cells <a href="https://www.ncbi.nlm.nih.gov/pubmed/19631389">recognise the same transplantation antigens</a> on the developing baby, and so support the process through which the embryo implants into the wall of the uterus and forms a healthy placenta and fetus.</p>
<p>So over time, repeated contact with the same male partner acts to <a href="http://esa-srb-2013.m.asnevents.com.au/schedule/session/1518/abstract/7382">stimulate and strengthen</a> a tolerant immune response to his transplantation antigens. The immune system of a woman responds to her partner’s seminal fluid to progressively build the chances of creating a healthy pregnancy over at least several months of regular sex. </p>
<p>Some forms of infertility and disorders of pregnancy are caused by immune rejection, when the process of tolerance is <a href="https://www.ncbi.nlm.nih.gov/pubmed/25023687">not adequately established</a>. </p>
<h2>Healthier pregnancy after months of sex</h2>
<p>A condition known as preeclampsia provides useful insights into how exposure to seminal fluid influences the success of pregnancy. <a href="https://www.betterhealth.vic.gov.au/health/healthyliving/pregnancy-pre-eclampsia">Preeclampsia</a> is an inflammatory disorder of pregnancy that compromises growth of the fetus, and often causes prematurity in babies. It can be life-threatening for mothers if left untreated. </p>
<p>Preeclampsia is more common when there has been limited sexual contact with the father before pregnancy is conceived, and is associated with <a href="https://www.ncbi.nlm.nih.gov/pubmed/20331588">insufficient establishment</a> of immune tolerance in the mother. </p>
<p>The length of time a couple have had a sexual relationship seems more important than the frequency of intercourse. In a <a href="https://www.ncbi.nlm.nih.gov/pubmed/19679359">study</a> of first pregnancies in 2507 Australian women, around 5% developed preeclampsia. Affected women were more than twice as likely to have had a short sexual relationship (less than six months) compared to the women who had healthy pregnancies. </p>
<p>Women with less than three months sexual activity with the conceiving partner had a 13% chance of preeclampsia, more than double the average occurrence. Among the few women who conceived on the first sexual contact with the father, the chance of preeclampsia was 22%, three times higher than the average. Low birth weight babies were also more common in this group. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/151359/original/image-20161222-17312-1f7bfqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/151359/original/image-20161222-17312-1f7bfqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/151359/original/image-20161222-17312-1f7bfqo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/151359/original/image-20161222-17312-1f7bfqo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/151359/original/image-20161222-17312-1f7bfqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/151359/original/image-20161222-17312-1f7bfqo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/151359/original/image-20161222-17312-1f7bfqo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Sperm swim in a soup of molecules that trigger an immune response in women.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/474203128?src=IWpjS5pr2oAjBHIBhebTIw-2-52&id=474203128&size=vector_eps">from www.shutterstock.com</a></span>
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<p>No relationship is observed between frequency of sexual activity during pregnancy and risk for preeclampsia, so it’s the <a href="https://www.ncbi.nlm.nih.gov/pubmed/12748491">duration of exposure</a> before conception that counts most.</p>
<p>Setting up a profile of immune tolerance that supports healthy pregnancy seems to be specific to the <a href="https://www.ncbi.nlm.nih.gov/pubmed/21529966">conceiving partner</a>. Women who change partners <a href="http://www.biomedsearch.com/nih/paternal-role-in-pre-eclampsia/22936817.html">return to a baseline state</a>, and must rebuild immune tolerance with the new partner.</p>
<p>Women who use <a href="https://www.ncbi.nlm.nih.gov/pubmed/2810672">barrier methods such as condoms or cervical caps</a> (which lower the exposure of the vagina and cervix to seminal fluid and sperm), and then conceive shortly after stopping contraception, have an <a href="https://www.ncbi.nlm.nih.gov/pubmed/12748491">elevated risk of preeclampsia</a>. </p>
<p>In contrast, women using an <a href="https://www.ncbi.nlm.nih.gov/pubmed/25854682">intrauterine device</a> before conception <a href="https://www.ncbi.nlm.nih.gov/pubmed/2810672">have been found</a> to have a slightly lower risk of preeclampsia.</p>
<h2>Sex during IVF can increase conception chances</h2>
<p>The importance of sex in creating the right environment for healthy pregnancy is also observed in clinical studies in IVF and other methods of assisted reproduction. Fertility is improved when couples have intercourse in the period when an embryo is transferred to the uterus. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/25281684">Combined data</a> from more than 2000 patients across seven studies showed the occurrence of a detectable pregnancy increased by 24% after vaginal contact with seminal fluid near the time of egg collection or embryo transfer. A <a href="https://www.ncbi.nlm.nih.gov/pubmed/11098040">study</a> of Australian and Spanish couples showed intercourse in the days just before or just after embryo transfer boosted pregnancy rates by 50%. </p>
<p>These studies focused on the early stages of pregnancy, with further research required to assess whether sexual intercourse influences rates of full term pregnancy after assisted reproduction. </p>
<p>Absence of exposure to seminal fluid may be one factor explaining why preeclampsia incidence is <a href="https://www.ncbi.nlm.nih.gov/pubmed/10469693">higher</a> after use of donated eggs or donor sperm, where prior female contact with the donor transplantation antigens has not occurred. The elevated risk after using donor semen <a href="https://www.ncbi.nlm.nih.gov/pubmed/19232411">can be reduced</a> if multiple prior insemination cycles take place with the same donor. </p>
<p>In couples who conceive using a modified version of IVF known as ICSI (intracytoplasmic sperm injection), preeclampsia incidence is also <a href="https://www.ncbi.nlm.nih.gov/pubmed/11879865">higher</a> in women who experience minimal exposure to their partner’s transplantation antigens due to very low sperm counts. </p>
<p>In some couples, an imbalance in seminal fluid composition or immune system factors may inhibit or slow down establishment of the <a href="https://www.ncbi.nlm.nih.gov/pubmed/27485480">tolerant immune profile in women</a>. In other couples, there may be immunological incompatibility that impairs tolerance, regardless of time spent together. </p>
<p>Maybe some couples may just <a href="https://www.ncbi.nlm.nih.gov/pubmed/22114108">need a little longer</a> having sex for pregnancy to occur. </p>
<h2>Immune system acts as a gatekeeper in pregnancy</h2>
<p>It is interesting to consider why the immune system is so closely involved in reproduction. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/20347158">One theory</a> is that females have evolved the ability to sense and respond to the signals in seminal fluid, in order to discern the quality or “fitness” of the male partner’s genetics. Scientists are now seeking to define the key signals on the male and female sides that promote tolerance. </p>
<p>Also, since male smoking, being overweight and other factors may shape <a href="https://www.ncbi.nlm.nih.gov/pubmed/27485480">how a woman responds to intercourse</a> in a biological sense, it helps explains why dad’s health is <a href="https://www.ncbi.nlm.nih.gov/pubmed/25124428">just as important</a> as that of the mother in preparing for pregnancy.</p><img src="https://counter.theconversation.com/content/67847/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Robertson receives funding from the National Health and Medical Research Council of Australia, and the Australian Research Council. </span></em></p>Health benefits come with regular sexual contact with the same male partner before pregnancy commences.Sarah Robertson, Professor and Director, Robinson Research Institute, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/407922015-05-01T14:57:13Z2015-05-01T14:57:13ZWhy infertility is becoming a public health issue in Europe<figure><img src="https://images.theconversation.com/files/79954/original/image-20150430-30729-mlkkit.jpg?ixlib=rb-1.1.0&rect=254%2C214%2C1508%2C1088&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Egg and spoon race.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/sexyeggs/7118478595/in/photolist-bR34Fz-61bQsq-6cF2wt-6uieUZ-8w8Pts-FRner-2UYLD-9RZUo5-9zXZvP-8U4iZw-69rtvB-5uTcek-9yhZfL-cMjwmQ-5cMyQt-qEW3EA-aa16qq-bCp1k2-sygzB-rzD8j3-6X4huN-a9nSfX-dGL2HN-rBQ7am-4AXT6n-7Ff8Fc-8axRxU-8auzZc-8FBYme-7jrQns-8FC5jg-7Ct7vS-62y5w1-8FC4mr-ckxYcd-62y5PW-5f8KEY-5f4jse-kpdwy-4MbCuP-gcuu7-62VpVG-cEj51s-2V8QoS-rktMNz-euFcQ1-qF9utK-c4bDTo-isqLf9-8oe3cp">Sexy Eggs</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Infertility is becoming a public health issue in Europe. Declining birth rates over the past 50 years mean that Europe is only <a href="http://www.institutdelors.eu/media/tgae20111itirkides.pdf?pdf=ok">producing 1.6 children per woman</a> – hardly satisfactory to compete on the global stage against increasing populations of fit and able youth from the emerging economies of India and China. And the problem is getting worse: couples reporting infertility in centres across Europe is increasing <a href="http://www.ncbi.nlm.nih.gov/pubmed/23842560">by 8-9% annually</a>.</p>
<p>Although the UK pioneered assisted reproductive technology (ART) such as IVF and artificial insemination in 1978, success rates are still as <a href="https://theconversation.com/desperate-couples-are-misled-by-only-positive-reports-of-ivf-20163">modest</a> as they were 35 years ago – <a href="http://www.ncbi.nlm.nih.gov/pubmed/25069504">only one in four couples</a> get the baby they so want. That said, up to 5% of children born in Europe <a href="http://www.sciencedirect.com/science/article/pii/S1472648312005901">are from ART</a>. But the fact is: if we want to exploit ART for societal growth, success rates need to improve.</p>
<h2>Diagnosing men</h2>
<p>One of the reasons for poor success is that we don’t diagnose the man carefully. One <a href="http://www.medicalnewstoday.com/articles/252824.php">third of couples</a> who are investigated for infertility is given a diagnosis of unexplained infertility but a study we conducted found that 80% of these cases <a href="http://www.dailymail.co.uk/health/article-2232989/MEN-blame-cases-unexplained-infertility--new-test-help-couples-succeed.html">were down to poor sperm quality</a>, also known as high sperm DNA damage. These couples are routinely given IVF – rather than the more advanced <a href="http://www.ucsfhealth.org/education/intracytoplasmic_sperm_injection/">intracytoplasmic sperm injection</a> (ICSI) where a single sperm is injected right into the egg – even though research shows that IVF success rates are even poorer than ICSI for this group of patients.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/79956/original/image-20150430-30735-1yuay9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/79956/original/image-20150430-30735-1yuay9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/79956/original/image-20150430-30735-1yuay9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/79956/original/image-20150430-30735-1yuay9d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/79956/original/image-20150430-30735-1yuay9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/79956/original/image-20150430-30735-1yuay9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/79956/original/image-20150430-30735-1yuay9d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The chosen ones.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-129449231/stock-photo-artificial-insemination.html?src=Bva09DlsQbi0dv8QxIJRHg-1-1">Egg by Shutterstock</a></span>
</figcaption>
</figure>
<p>Another reason is that, although infertility is recognised as a disease (as opposed to a lifestyle choice), only 40% of fertility treatment is performed in the public sector with minimal funding. <a href="http://www.britishandrology.org.uk/spring-summer-2009-newsletter/">Less than 1% of research council budgets</a> is allocated to it. </p>
<p>In 2008, the European Parliament <a href="http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+WQ+E-2009-0201+0+DOC+XML+V0//EN">called on</a> “all member states to ensure the right of couples to universal access to infertility treatment”. This has not been implemented. In the UK, the National Institute for Health and Care Excellence (NICE) recommends that three cycles of IVF should be given to those eligible. This has not been implemented either. In fact, availability to NHS-funded treatment in the UK <a href="http://www.fertilityfairness.co.uk/">is a postcode lottery</a>.</p>
<p>As a scientist working in this field for the past 20 years, my concern goes beyond this injustice. I believe that a focus on infertility, coupled with an improvement in ART could provide us with an unrivalled opportunity to discover the earliest pathways by which genetic causes across generations and epigenetic illness – where our environment and lifestyle <a href="https://theconversation.com/how-your-grandparents-life-could-have-changed-your-genes-19136">can alter gene behaviour</a> – should be exploited and improved for society’s benefit. </p>
<p>This is particularly pertinent today as we now know that our reproductive health is <a href="http://rstb.royalsocietypublishing.org/content/365/1546/1697">under further environmental threat</a> from bio-toxins, pharmaceuticals and personal care products. Poor lifestyle choices are also leading to the latest health burden epidemics of obesity and association with <a href="http://www.patient.co.uk/doctor/diabetes-mellitus">diabetes mellitus</a>, which in turn further <a href="http://bit.ly/1JUou2J">impairs fertility</a>. </p>
<h2>Genetic causes</h2>
<p>Until recently, however, we believed that birth rates had fallen over such a short time because of direct lifestyle and environmental causes rather than genetics. But we are changing our minds. Data is now accumulating to show that these lifestyle hazards <a href="http://pure.qub.ac.uk/portal/en/publications/the-paternal-genome-and-the-health-of-the-assisted-reproductive-technology-child%283c1cbe2d-1f20-4ae6-afcb-6b1dd0ac9a30%29.html">can cause genetic and epigenetic burdens</a> that are then passed on to our offspring and their offspring. Worry indeed. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/79955/original/image-20150430-30721-2d8w9m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/79955/original/image-20150430-30721-2d8w9m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=426&fit=crop&dpr=1 600w, https://images.theconversation.com/files/79955/original/image-20150430-30721-2d8w9m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=426&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/79955/original/image-20150430-30721-2d8w9m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=426&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/79955/original/image-20150430-30721-2d8w9m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=535&fit=crop&dpr=1 754w, https://images.theconversation.com/files/79955/original/image-20150430-30721-2d8w9m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=535&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/79955/original/image-20150430-30721-2d8w9m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=535&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Slim pickings.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/82066314@N06/10384448133/in/photolist-gPD1Dc-5Ldkr3-8DFUR5-5L97rZ-tifho-qdRzcd-f4YbSu-9RWZCx-34s9vM-5pWtcQ-4xz9xD-CXTCf-92Pdjn-naamtn-6ihef-62y6C9-9pvFRP-az4SG-f6dmr4-62y6JC-tifhp-dXiEf1-83GTn3-6eSBar-7zFjM9-7zBx1X-dPCqaS-62y61o-62y5YC-2gkXp-qckuLy-azLbRG-7zFjmW-5fqbFy-9dS4Te-bjUohx-2gkVy-7zFizm-4iEZ1E-7zFiY7-62tRrZ-c5iLLE-3ApXR-4wRoyT-4wRnuZ-4wRn4T-7zE94g-tifhh-62gYJG-9CgwzH">Iqbal Osman</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>In laboratory terms, we should start with studies on the paternal gamete – the sperm that a man produces in vast numbers from puberty to senility. It is more useful than the female gamete (the egg) for several reasons. There is more choice for an egg as to which sperm fertilises it and there are more opportunities for therapy because sperm is produced in large numbers. It can also be more easily accessed. </p>
<p>Investing in the improvement of ART success is a an effective way of increasing our birth rates, which we know also increases our economic health and improves the health of future generations. We also have more of a shot at helping the expanding group of couples whom we currently try and fail to help to have their much longed-for family.</p><img src="https://counter.theconversation.com/content/40792/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sheena Lewis is Managing Director and receives funding from Lewis Fertility Testing Ltd, a spin out company from Queen's University
</span></em></p>A declining birth rate and treatment that still has a modest success rate calls for better ways to investigate infertility.Sheena Lewis, Professor of Reproductive Medicine, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/70762012-05-22T20:23:47Z2012-05-22T20:23:47ZNo need for alarm about birth defects after assisted conception<figure><img src="https://images.theconversation.com/files/10925/original/dhrrz8gg-1337661714.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Millions of babies have been born after the use of assisted reproductive technologies, and nothing has gone wrong with the vast majority.</span> <span class="attribution"><span class="source">Chiceaux Lynch</span></span></figcaption></figure><p>Some people may be wondering whether it’s wise to undergo assisted reproduction after <a href="https://theconversation.com/does-all-assisted-reproduction-lead-to-birth-defects-6898">recent media headlines</a> about these technologies increasing the risk of birth defects. In fact, millions of babies have now been born worldwide after use of assisted reproductive technologies, and nothing has gone wrong with the vast majority.</p>
<p>The technologies used to help people conceive are mainly in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). <a href="http://www.varta.org.au/brochures-and-pamphlets/w1/i1003349/">In IVF</a>, the woman’s eggs are collected, as is sperm from the male partner or donor. Both are left in a culture dish in a laboratory to allow the egg to be fertilized by the sperm.</p>
<p>ICSI involves use of a single sperm to inseminate the egg, not millions of sperm as are used in conventional IVF. This procedure is often used when the male produces small numbers of sperm or when conventional IVF has not worked for unknown reasons.</p>
<p>There have been <a href="http://humrep.oxfordjournals.org/content/20/2/328.full">many studies</a> in Australia and <a href="http://ije.oxfordjournals.org/content/34/3/696.full">overseas</a> designed to assess the safety of these technologies. It’s generally found that about one in 20 babies conceived naturally will have a birth defect. And, if IVF or ICSI is used to conceive, the risk of defects goes up – but by not very much.</p>
<p>In a recent <a href="http://humrep.oxfordjournals.org/content/25/1/59.long">Victorian study</a> of 3,312 IVF and 3,634 ICSI pregnancies with a single baby rather than twins, we found the risk of birth defects was slightly higher for ICSI (one in 15) than for IVF (one in 16). So for every 100 babies conceived with use of either IVF or ICSI, 93 or 94 will not have a birth defect.</p>
<p>We didn’t find the difference between outcomes for IVF and ICSI that the <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1008095">South Australian study</a> responsible for recent headlines did. Neither have many other people who have done research in this area. </p>
<p>In fact, the SA study’s finding of an increased risk after ICSI (but not IVF) is unexpected and difficult to explain. Their numbers were not as large as ours for IVF and ICSI and they lumped together many minor defects with the more severe ones.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/10848/original/47qmwhfz-1337563380.jpg?ixlib=rb-1.1.0&rect=0%2C9%2C800%2C493&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/10848/original/47qmwhfz-1337563380.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/10848/original/47qmwhfz-1337563380.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/10848/original/47qmwhfz-1337563380.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/10848/original/47qmwhfz-1337563380.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/10848/original/47qmwhfz-1337563380.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/10848/original/47qmwhfz-1337563380.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Ekem/Wikimedia Commons</span></span>
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</figure>
<p>Unlike the SA study, <a href="http://ije.oxfordjournals.org/content/34/3/696.full">other researchers</a> have concluded that the micro-injection procedure used in ICSI to mix a single sperm with an egg, didn’t add to the risk of the fetus having a birth defect over and above that associated with IVF. </p>
<p>The Victorian study was large enough to allow for examination of specific types of birth defects after IVF and ICSI. We found that there was a particular group of birth defects occurring and they were ones that formed during the first four weeks of pregnancy, before organs start developing. These are called blastogenesis defects and can affect the formation and fusion of the spine, the gastrointestinal tract (gut) and other parts of the body.</p>
<p>The frequency with which these specific defects usually occur is very low, but can be as high as one in 110 babies after assisted reproduction. What seems to reduce this risk and the risk of other birth defects is the timing of the embryo transfer from the laboratory to the woman’s uterus. </p>
<p>Our study showed very clearly that a fresh embryo transfer (usually occurring within days of the egg pick-up for IVF or ICSI) carried a far greater risk of birth defects than an embryo that had been frozen and thawed prior to transfer. Thawed embryo transfer usually occurs in a natural menstrual cycle, months after the egg-pick up – well beyond the time when all the hormones required to retrieve the eggs for IVF or ICSI have disappeared from a woman’s body. </p>
<p>The frequency of blastogenesis defects with a fresh embryo transfer was one in 100 but if a thawed transfer was used, only one in 250 births was affected.</p>
<p>People seeking treatment to improve their chance of having a baby need to be aware of the slightly increased risk of birth defects. Australian data are providing strong evidence for the use of embryos that have been frozen after IVF and then thawed before their transfer to the womb. At the moment, there’s not very convincing evidence to suggest that IVF is safer than ICSI, so expect to hear more.</p><img src="https://counter.theconversation.com/content/7076/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jane Halliday is an NHMRC Senior Research Fellow.</span></em></p>Some people may be wondering whether it’s wise to undergo assisted reproduction after recent media headlines about these technologies increasing the risk of birth defects. In fact, millions of babies have…Jane Halliday, Associate Professor in public health genetics, Murdoch Children's Research InstituteLicensed as Creative Commons – attribution, no derivatives.