Fertility and Sterility On Air

Welcome to Fertility and Sterility On Air - the podcast where you can stay current on the latest global research in the field of Reproductive Medicine. This podcast brings you an overview of the monthly F&S journal, in depth discussion with authors, and other special features.

Fertility and Sterility On Air - TOC: July 2025 07/13/2025

Fertility and Sterility On Air - Unplugged: May 2025 06/29/2025

Fertility and Sterility On Air - Live from the PCRS 2025 Annual Meeting 06/22/2025

Fertility and Sterility On Air - Editors in Chief Bonus Episode 06/15/2025

Fertility and Sterility On Air - TOC: June 2025 06/08/2025

Fertility and Sterility On Air - Seminal Article: Julia DiTosto and Sunni Mumford 06/01/2025

Fertility and Sterility On Air - TOC: May 2025 05/11/2025

Fertility and Sterility On Air - Best of ASRM and ESHRE 2025 05/04/2025

Fertility and Sterility On Air - Live from AAGL 2024: Joint AAGL/ASRM Podcast 05/03/2025

Fertility & Sterility On Air - Unplugged Micro-Episode: F&S Reports Special Issue with Dr. Pierre Comizzoli and Dr. Richard Paulson 04/27/2025

Fertility and Sterility On Air - Unplugged: March 2025 04/20/2025

Fertility and Sterility On Air - TOC: April 2025 04/06/2025

Fertility and Sterility On Air - TOC: March 2025 03/16/2025

Fertility and Sterility On Air - TOC: Feb 2025 02/16/2025

Fertility and Sterility On Air - TOC: Jan 2025 02/09/2025

Fertility and Sterility On Air - TOC: Dec 2024 01/19/2025

Fertility and Sterility On Air - TOC: November 2024 12/22/2024

Fertility and Sterility On Air - Unplugged: December 2024 12/15/2024

Fertility and Sterility On Air - TOC: October 2024 12/01/2024

Fertility and Sterility On Air - Live from ASRM 2024: Part 2 11/17/2024

Fertility and Sterility On Air - Live from ASRM 2024: Part 1 11/17/2024

Fertility and Sterility On Air - TOC: September 2024 11/03/2024

Fertility and Sterility On Air - Unplugged: October 2024 10/20/2024

Fertility and Sterility On Air - Unplugged: September 2024 09/22/2024

Fertility and Sterility On Air - TOC: August 2024 09/15/2024

Fertility and Sterility On Air - Live from ESHRE 2024: Part 2 09/08/2024

Fertility and Sterility On Air - Live from ESHRE 2024: Part 1 09/08/2024

Fertility and Sterility On Air - ANZSREI 2024 Journal Club Global: "Should Unexplained infertility Go Straight to IVF?" 09/01/2024

Fertility and Sterility On Air - ANZSREI 2024 Journal Club Global: "Should Unexplained infertility Go Straight to IVF?" Presented in partnership with Fertility and Sterility onsite at the 2024 ANZSREI meeting in Sydney, Australia. The ANZSREI 2024 debate discussed whether patients with unexplained infertility should go straight to IVF. Experts on both sides weighed the effectiveness, cost, and psychological impact of IVF versus alternatives like IUI. The pro side emphasized IVF's high success rates and diagnostic value, while the con side argued for less invasive, cost-effective options. The debate highlighted the need for individualized care, with no clear consensus reached among the audience. View Fertility and Sterility at TRANSCRIPT: Welcome to Fertility and Sterility On Air, the podcast where you can stay current on the latest global research in the field of reproductive medicine. This podcast brings you an overview of this month's journal, in-depth discussion with authors, and other special features. F&S On Air is brought to you by Fertility and Sterility family of journals in conjunction with the American Society for Reproductive Medicine, and is hosted by Dr. Kurt Barnhart, Editor-in-Chief, Dr. Eve Feinberg, Editorial Editor, Dr. Micah Hill, Media Editor, and Dr. Pietro Bordoletto, Interactive Associate-in-Chief. I'd just like to say welcome to our third and final day of the ANZSREI conference. We've got our now traditional F&S podcast where we've got an expert panel, we've got our international speaker, Pietro, and we've got a wonderful debate ahead of us. This is all being recorded. You're welcome, and please think of questions to ask the panel at the end, because it's quite an interactive session, and we're going to get some of the best advice on some of the really controversial areas, like unexplained infertility. Hi, everyone. Welcome to the second annual Fertility and Sterility Journal Club Global, coming to you live from the Australia and New Zealand Society for Reproductive Endocrinology and Infertility meeting. I think I speak on behalf of everyone at F&S that we are so delighted to be here. Over the last two years, we've really made a concerted effort to take the podcast on the road, and this, I think, is a nice continuation of that. For the folks who are tuning in from home and listening to this podcast after the fact, the Australia and New Zealand Society for Reproductive Endocrinology is a group of over 100 certified reproductive endocrinologists across Australia and New Zealand, and this is their annual meeting live in Sydney, Australia. Today's debate is a topic that I think has vexed a lot of individuals, a lot of patients, a lot of professional groups. There's a fair amount of disagreement, and today we're going to try to unpack a little bit of unexplained infertility, and the question really is, should we be going straight to IVF? As always, we try to anchor to literature, and there are two wonderful documents in fertility and sterility that we'll be using as our guide for discussion today. The first one is a wonderful series that was published just a few months ago in the May issue, 2024, that is a views and reviews section, which means there's a series of three to five articles that kind of dig into this topic in depth. And the second article is our professional society guideline, the ASRM Committee Opinion, entitled Evidence-Based Treatments for Couples with Unexplained Infertility, a guideline. The format for today's discussion is debate style. We have a group of six experts, and I've asked them to randomly assign themselves to a pro and a con side. So I'll make the caveat here that the things that they may be saying, positions they may be trying to influence us on, are not necessarily things that they believe in their academic or clinical life, but for the purposes of a rich debate, they're going to have to be pretty deliberate in convincing us otherwise. I want to introduce my panel for today. We have on my immediate right, Dr. Raewyn Tierney. She's my co-moderator for tonight, and she's a practicing board-certified fertility specialist at IVF Australia. And on my immediate left, we have the con side. Going from left to right, Dr. Michelle Quick, practicing board-certified fertility specialist at IVF Australia. Dr. Robert LaHood, board-certified reproductive endocrinologist and clinical director of IVF Australia here in Sydney. And Dr. Clara Bothroyd, medical director at Care Fertility and the current president of the Asia Pacific Initiative in Reproduction. Welcome. On the pro side, going from right to left, I have Dr. Aurelia Liu. She is a practicing board-certified fertility specialist, medical director of Women's Health Melbourne, and clinical director at Life Fertility in Melbourne. Dr. Marcin Stankiewicz, a practicing board-certified fertility specialist and medical director at Family Fertility Centre in Adelaide. And finally, but certainly not least, the one who came with a tie this morning, Dr. Roger Hart, who is a professor of reproductive medicine at the University of Western Australia and the national medical director of City Fertility. Welcome, pro side. Thank you. I feel naked without it. APPLAUSE I've asked both sides to prepare opening arguments. Think of this like a legal case. We want to hear from the defence, we want to hear from the plaintiffs, and I'm going to start with our pro side. I'd like to give them a few minutes to each kind of introduce their salient points for why we should be starting with IVF for patients with unexplained infertility. Thanks, Pietro. To provide a diagnosis of unexplained infertility, it's really a reflection of the degree investigation we've undertaken. I believe we all understand that unexplained infertility is diagnosed in the presence of adequate intercourse, normal semen parameters, an absence ovulatory disorder, patent fallopian tubes, and a normal detailed pelvic ultrasound examination. Now, the opposing team will try to convince you that I have not investigated the couple adequately. Personally, I'm affronted by that suggestion. But what possible causes of infertility have I not investigated? We cannot assess easily sperm fertilising capability, we cannot assess oocyte quality, oocyte fertilisation potential, embryonic development, euploidy rate, and implantation potential. Surely these causes of unexplained fertility will only become evident during an IVF cycle. As IVF is often diagnostic, it's also a therapeutic intervention. Now, I hear you cry, what about endometriosis? And I agree, what about endometriosis? Remember, we're discussing unexplained infertility here. Yes, there is very good evidence that laparoscopic treatment for symptomatic patients with endometriosis improves pelvic pain, but there is scant evidence that a diagnostic laparoscopy and treating any minor disease in the absence of pain symptoms will improve the chance of natural conception, or to that matter, improve the ultimate success of IVF. Indeed, in the absence of endometriomas, there is no negative impact on the serum AMH level in women with endometriosis who have not undergone surgery. Furthermore, there is no influence on the number of oocytes collected in an IVF cycle, the rate of embryonic aneuploidy, and the live birth rate after embryo transfer. So why put the woman through a painful, possibly expensive operation with its attendant risks as you're actually delaying her going straight to IVF? What do esteemed societies say about a diagnostic laparoscopy in the setting of unexplained infertility? The ESHRE guidelines state routine diagnostic laparoscopy is not recommended for the diagnosis of unexplained infertility. Indeed, our own ANZSREI consensus statement says that for a woman with a minimal and mild endometriosis, that the number of women needed to treat for one additional ongoing pregnancy is between 3 and 100 women with endometriosis. Is that reasonable to put an asymptomatic woman through a laparoscopy for that limited potential benefit? Now, regarding the guidelines for unexplained infertility, I agree the ASRM guidelines do not support IVF as a first-line therapy for unexplained infertility for women under 37 years of age. What they should say, and they don't, is that it is assumed that she is trying for her last child. There's no doubt if this is her last child, if it isn't her last child, sorry, she will be returning, seeking treatment, now over 37 years of age, where the guidelines do state there is good evidence that going straight to IVF may be associated with higher pregnancy rates, a shorter time to pregnancy, as opposed to other strategies. They then state it's important to note that many of these included studies were conducted in an area of low IVF success rates than those currently observed, which may alter this approach, suggesting they do not even endorse their own recommendations. The UK NICE guidelines, what do they say for unexplained infertility? Go straight to IVF. So while you're listening to my esteemed colleagues on my left speaking against the motion, I'd like to be thinking about other important factors that my colleagues on my right will discuss in more detail. Consider the superior efficacy of IVF versus IUI, the excellent safety profile of IVF and its cost-effectiveness. Further, other factors favouring a direct approach to IVF in the setting of unexplained infertility are what is the woman's desired family? We should not be focusing on her first child, we should be focusing on giving her the family that she desires and how we can minimise her inconvenience during treatment, as this has social, career and financial consequences for those impediments for her while we attempt to help her achieve her desired family. Thank you. APPLAUSE I think the young crowd would say that that was shots fired. LAUGHTER Con side? We're going to save the rebuttal for the time you've allocated to that, but first I want to put the case about unexplained infertility. Unexplained infertility in 2024 is very different to what it was 10 and 20 years ago when many of the randomised controlled trials that investigated unexplained infertility were performed. The armamentarium of investigative procedures and options that we have has changed, as indeed has our understanding of the mechanisms of infertility. So much so that that old definition of normal semen analysis, normal pelvis and ovulatory, which I think was in Roy Homburg's day, is now no longer fit for purpose as a definition of unexplained infertility. And I commend to you ICMART's very long definition of unexplained infertility, which really relies on a whole lot of things, which I'm going to now take you through what we need to do. It is said, or was said, that 30% of infertility was unexplained. I think it's way, way less than that if we actually look at our patients, both of them, carefully with history and examination and directed tests, and you will probably reduce that to about 3%. Let me take you through female age first. Now, in the old trials, some of the women recruited were as old as 42. That is not unexplained infertility. We know about oocyte aneuploidy and female ageing. 41, it's not unexplained. 40, it's not unexplained. 39, it's not unexplained. And I would put it to you that the cut-off where you start to see oocyte aneuploidy significantly constraining fertility is probably 35. So unexplained infertility has to, by definition, be a woman who is less than 35. I put that to you. Now, let's look at the male. Now, what do we know about the male, the effect of male age on fertility? We know that if the woman is over 35, and this is beautiful work that's really done many years ago in Europe, that if the woman is over 35 and the male is five years older than her, her chance of natural conception is reduced by a further 30%. So I put it to you that, therefore, the male age is relevant. And if she's 35 and has a partner who's 35 years older than her or more, it's not unexplained infertility. It's related to couple age. Now, we're going to... So that's age. Now, my colleagues are going to take you through a number of treatment interventions other than IVF, which we can do with good effect if we actually make the diagnosis and don't put them into the category of unexplained infertility. You will remember from the old trials that mild or moderate or mild or minimal endometriosis was often included, as was mild male factor or seminal fluid abnormalities. These were really multifactorial infertility, and I think that's the take-home message, that much of what we call unexplained is multifactorial. You have two minor components that act to reduce natural fecundability. So I now just want to take you through some of the diagnoses that contribute to infertility that we may not, in our routine laparoscopy and workup, we may not pick up and have previously been called unexplained infertility. For instance, we know that adenomyosis is probably one of the mechanisms by which endometriosis contributes to infertility. Chronic endometritis is now emerging as an operative factor in infertility, and that will not be diagnosed easily. Mild or minimal endometriosis, my colleagues will cover. The mid-cycle scan will lead you to the thin endometrium, which may be due to unexpected adhesive disease, but also a thin endometrium, which we know has a very adverse prognostic factor, may be due to long-term progestin contraception. We are starting to see this emerge. Secondary infertility after a caesarean section may be due to an isthma seal, and we won't recognise that unless we do mid-cycle scans. That's the female. Let's look at the male. We know now that seminal fluid analysis is not a good predictor of male fertility, and there is now evidence from Ranjith Ramasamy's work that we are missing clinical varicoceles because we failed to examine the male partner. My colleagues will talk more about that. We may miss DNA fragmentation, which again may contribute via the basic seminal fluid analysis. Now, most of these diagnoses can be made or sorted out or excluded within one or two months of your detailed assessment of both partners by history and examination. So it's not straight to IVF, ladies and gentlemen. It's just a little digression, a little lay-by, where you actually assess the patient thoroughly. She did not need a tie for that rebuttal. LAUGHTER Prasad. Thank you. Well, following from what Professor Hart has said, I'm going to show that IVF should be a go-to option because of its effectiveness, cost-effectiveness and safety. Now, let me first talk about the effectiveness, and as this is an interaction session, I would like to ask the audience, please, by show of hands, to show me how many of you would accept a medical treatment or buy a new incubator if it had a 94% chance of failure? Well, let the moderator please note that no hands have been raised. Thank you very much. Yet, the chance of live birth in Australian population following IUI is 6%, where, after IVF, the live birth is 40%. Almost seven times more. Now, why would we subject our patients to something we ourselves would not choose? Similarly, findings were reported from international studies that the hazard ratio of 1.25 favouring immediate IVF, and I will talk later about why it is important from a safety perspective. Cost-effectiveness. And I quote ESHRE guidelines. The costs, treatment options have not been subject to robust evaluations. Now, again, I would like to ask the audience, this time it's an easy question, how many of you would accept as standard an ongoing pregnancy rate of at least 38% for an average IVF cycle? Yeah, hands up. All right, I've got three-quarters of the room. OK. Well, I could really rest my case now, as we have good evidence that if a clinic has got an ongoing pregnancy rate of 38% or higher with IVF with single embryo transfer, then it is more effective, more cost-effective, and should be a treatment of choice. And that evidence comes from the authors that are sitting in this room. Again, what would the patients do? If the patients are paying for the treatment, would they do IUI? Most of them would actually go straight to IVF. And we also have very nice guidelines which advise against IUI based on cost-effectiveness. Another factor to mention briefly is the multiple births, which cost five to 20 times more than singleton. The neonatal cost of a twin birth costs about five times more than singletons, and pregnancy with delivery of triplets or more costs nearly 20 times. Now, the costs that I'm going to quote are in American dollars and from some time ago, from Fertility and Sterility. However, the total adjusted all healthcare costs for a single-dom delivery is about US$21,000, US$105,000 for twins, and US$400,000 for triplets and more. Then the very, very important is the psychological cost of the high risk of failure with IUI. Now, it is well established that infertility has a psychological impact on our patients. Studies have shown that prolonged time to conception extends stress, anxiety, and depression, and sexual functioning is significantly negatively impacted. Literature shows that 56% of women and 32% of men undergoing fertility treatment report significant symptoms of depression, and 76% of women and 61% of men report significant symptoms of anxiety. Shockingly, it is reported that 9.4% of women reported having suicidal thoughts or attempts. The longer the treatment takes, the more our patients display symptoms of distress, depression, and anxiety. Safety. Again, ESHRE guideline says the safety of treatment options have not been subjected to robust evaluation. But let me talk you through it. In our Australian expert hands, IVF is safe, with the risk of complications of ectopic being about 1 in 1,500 and other risks 1 in 3,000. However, let's think for a moment on impact of multiple births. A multiple pregnancy has significant psychological, physical, social, and financial consequences, which I can go further into details if required. I just want to mention that the stillbirth rate increases from under 1% for singleton pregnancies to 4.5% for twins and 8.3% for higher-order multiples, and that multiple pregnancies have potential long-term adverse health outcomes for the offspring, such as the increased risk of health issues through their life, increased learning difficulties, language delay, and attention and behavior problems. The lifelong disability is over 25% for babies weighing less than 1 kilogram at delivery. And please note that the quoted multiple pregnancy rates with IUI can reach up to 33%, although in expert hands it's usually around 15%, which is significantly higher than single embryo transfer. In conclusion, from the mother and child safety perspective, for the reason of medical efficacy and cost effectiveness, we have reasons to believe you should go straight to IVF. We're going to be doing these debates more often from Australia. This is a great panel. One side, please. Unexplained infertility. My colleagues were comparing IUI ovulation induction with IVF, but there are other ways of achieving pregnancies with unexplained fertility. I'm going to take the patient's perspective a little bit here. It's all about shared decision-making, so the patient needs to be involved in the decision-making. And it's quite clear from all the data that many patients with unexplained infertility will fall pregnant naturally by themselves even if you do nothing. So sometimes there's definitely a place in doing nothing, and the patient needs to be aware of that. So it's all about informed consent. How do we inform the patient? So we've got to make a proper diagnosis, as my colleague Dr. Boothright has already mentioned, and just to jump into IVF because it's cost-effective is not doing our patients a justice. The prognosis is really, really important, and even after 20 years of doing this, it's all about the duration of infertility, the age of the patient, and discussing that... /episode/index/show/fertilityandsterilityonair/id/32760922

Fertility and Sterility On Air - Unplugged: August 2024 08/11/2024

Fertility and Sterility On Air - TOC: July 2024 08/04/2024

Fertility and Sterility On Air

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