Fresh Embryo Transfer Yields Higher Live Birth Rates Than Freeze-All Strategy in Women with Low IVF Prognosis: Study

China: A randomized clinical trial conducted at fertility centers in China assessed live birth rates following fresh versus frozen embryo transfers in women with a low probability of in vitro fertilization (IVF) success. Published in The BMJ, the study found that 40% of women who underwent fresh embryo transfer had a viable live birth, compared to 32% in the frozen embryo transfer group. The fresh transfer group demonstrated higher pregnancy rates and a greater cumulative live birth rate within one year of randomization.

The approach of freezing all viable embryos before transferring them to the uterus, known as the “freeze-all strategy,” has gained widespread use in in vitro fertilization over the past decade. However, it may not be the most suitable option for everyone. Considering this, Daimin Wei, Key Laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University, Jinan, China, and colleagues aimed to evaluate whether a freeze-all strategy enhances the likelihood of live birth compared to fresh embryo transfer in women with a low prognosis for IVF treatment.

For this purpose, the researchers conducted a multicentre, randomised controlled trial across nine fertility centers in China, involving 838 women with a low IVF prognosis. Participants, defined by poor ovarian reserve or retrieval of ≤9 oocytes, were randomly assigned to either a frozen or fresh embryo transfer group. The frozen group underwent embryo cryopreservation for later transfer, while the fresh group received embryo transfer immediately after oocyte retrieval.

The primary outcome was live birth at ≥28 weeks gestation. The secondary outcomes included clinical pregnancy rates, pregnancy loss, ectopic pregnancy, birth weight, maternal and neonatal complications, and cumulative live birth rates within one year of randomisation.

The key findings of the study were as follows:

  • The live birth rate was lower in the frozen embryo transfer group (32%, 132 of 419) than in the fresh embryo transfer group (40%, 168 of 419) (relative ratio: 0.79).
  • The clinical pregnancy rate was lower in the frozen embryo transfer group (39%, 164 of 419) compared to the fresh embryo transfer group (47%, 197 of 419) (relative ratio: 0.83).
  • The cumulative live birth rate was lower in the frozen embryo transfer group (44%, 185 of 419) than in the fresh embryo transfer group (51%, 215 of 419) (relative ratio: 0.86).
  • No significant differences were observed in birth weight, obstetric complications, or neonatal morbidities between the two groups.

The researchers found that fresh embryo transfer may be a more suitable option for women with a low prognosis for IVF, as it resulted in a higher live birth rate compared to the freeze-all strategy. Unlike previous findings in women with a good prognosis, this study demonstrated that a freeze-all approach led to lower live birth rates in this specific patient group.

“The results do not support the routine use of the freeze-all strategy in women with a low prognosis. To determine their impact on reproductive outcomes, further research is needed to evaluate treatment strategies that delay fresh embryo transfer, such as accumulating embryos through back-to-back cycles or performing routine preimplantation genetic testing for aneuploidy,” the researchers concluded.

Reference:

Wei D, Sun Y, Zhao H, Yan J, Zhou H, Gong F, Zhang A, Wang Z, Jin L, Bao H, Zhao S, Xiao Z, Qin Y, Geng L, Cui L, Sheng Y, Sun M, Liu P, Ding L, Liu H, Wu K, Li Y, Lu Y, Xu B, Xu B, Zhang L, Zhang H, Legro RS, Chen ZJ. Frozen versus fresh embryo transfer in women with low prognosis for in vitro fertilisation treatment: pragmatic, multicentre, randomised controlled trial. BMJ. 2025 Jan 29;388:e081474. doi: 10.1136/bmj-2024-081474. PMID: 39880462; PMCID: PMC11778674.

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Women with Non-Malignant Gynecological Diseases Face Increased Cardiovascular and Cerebrovascular Risk: Study Finds

Australia: A new systematic review and meta-analysis of over 3.2 million individuals has revealed a potential link between non-malignant gynecological diseases (NMGDs) and an increased risk of cardiovascular or cerebrovascular disease (C/CVD).

“Non-malignant gynecological diseases were linked to a 28% higher risk of cardiovascular or cerebrovascular disease (SRR = 1.28). The risk was even more pronounced for ischemic heart disease, with a 41% increase, especially in individuals with endometriosis and polycystic ovary syndrome,” the researchers reported in the BMJ Journal Heart. These findings highlight the importance of cardiovascular risk assessment in women with NMGDs.

The researchers note that cardiovascular disease remains the leading cause of death worldwide. Non-malignant gynecological diseases impact overall health and well-being and contribute to an increased risk of cardiovascular or cerebrovascular disease, emphasizing the need for further investigation into this potential association. To fill this knowledge gap, Giorgia Elisabeth Colombo, Department of Obstetrics and Gynecology, Ospedale Regionale di Lugano, Lugano, Switzerland, and colleagues aimed to compile all available epidemiological studies on the link between chronic NMGD and C/CVD. As the first meta-analysis on this association, it offers novel and comprehensive insights into the overall relationship and subgroup-specific risks.

For this purpose, the researchers conducted a comprehensive search across seven databases for relevant studies up to April 21, 2024. They included observational studies that reported risk estimates for the association between NMGD and C/CVD. Two independent reviewers extracted the data, and random effects models were used to calculate the summary relative risk (SRR). The composite C/CVD outcome included ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease. Study quality and risk of bias were assessed using the ROBINS-I tool.

Key Findings:

  • A total of 6,639 studies were screened, out of which 59 were reviewed in full, and 28 were included in the final analysis, covering 3,271,242 individuals.
  • More than half (53.5%) of the studies were assessed as having a ‘serious’ or ‘critical’ risk of bias.
  • Individuals with NMGD had a significantly higher risk of composite C/CVD, with low heterogeneity among studies (SRR 1.28; n=16 studies, I²=65.3%).
  • The risk of ischemic heart disease was elevated (SRR 1.41; n=21 studies, I²=73.7%).
  • The likelihood of cerebrovascular disease was also increased (SRR 1.33; n=16 studies, I²=91.5%).
  • Subgroup analyses revealed a higher risk of C/CVD and its components in individuals with a history of endometriosis or polycystic ovary syndrome.

The researchers found a significant association between NMGD and C/CVD across all studies, though individual estimates varied. They emphasized the need for rigorous study designs, better harmonization of NMGD and C/CVD definitions, and a deeper understanding of risk variations among subpopulations. Highlighting the clinical relevance, the researchers urged physicians to consider this association for early risk assessment and prevention strategies.

“Our findings emphasize the necessity of prospective longitudinal research to further evaluate these risks, which could drive the development of targeted primary prevention strategies and improve patient outcomes,” they concluded.

Reference:

Colombo GE, Mahamat-Saleh Y, Armour M, Madan K, Sabag A, Kvaskoff M, Missmer SA, Condous G, Pathan F, Leonardi M. Non-malignant gynaecological disease and risk of cardiovascular or cerebrovascular disease: a systematic review and meta-analysis. Heart. 2025 Feb 24:heartjnl-2024-324675. doi: 10.1136/heartjnl-2024-324675. Epub ahead of print. PMID: 39993911.

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Contraction inhibitors after 30 weeks have no effect on baby’s health, reveals research

The use of tocolytic drugs in cases of threatened premature birth after 30 weeks of pregnancy does not improve the baby’s health. This is shown by the largest study concerning the effectiveness of tocolytic drugs on the health of babies, led by Amsterdam UMC, the results of which were published today in The Lancet.

Worldwide, 1 in 10 pregnancies result in premature birth. Children born prematurely face a higher risk of mortality and serious health problems, both in the short and long term. As a results, tocolytic drugs have been used a standard treatment for many years in women who threaten to given birth prematurely, after 24 weeks and before 34 weeks of gestation. The rationale behind their use is that prolonging pregnancy grants the baby with extra time to develop, thereby reducing the risk of health problems.

“Whether prolongation of pregnancy by using tocolytic drugs actually benefits the health of the baby has not been substantiated by research until now,” says

Martijn Oudijk, professor of prevention and treatment of premature birth at Amsterdam UMC.

The study, funded by the ZonMw programme Good Use of Medicines, was conducted in twenty-four Dutch hospitals that are part of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology, as well as two hospitals in England and Ireland. The study involved 755 women with threatened premature labour (TPL) between 30 and 34 weeks of pregnancy, half of whom received a tocolytic drug, while the other half received a placebo.

“This is the largest placebo-controlled study ever performed investigating the effects of tocolytic drugs on the baby’s health. Our results showed no difference whatsoever. There was no benefit but also no harm done,” says Amsterdam UMC PhD-student Larissa van der Windt.

According to Oudijk, it is time to reconsider current medical practice: “We have to ask ourselves whether tocolytic drugs should continue to be a standard treatment for TPL after 30 weeks of pregnancy. The purpose of delaying childbirth is to give newborns a better start and improve their health. Premature birth often has a medical cause, such as an infection or problems with the placenta. A prolonged stay in the uterus longer might actually be harmful.”

In large hospitals in Canada and Ireland, the use of tocolytic drugs after 30 weeks of pregnancy has already been discontinued. “It is high time that we start working on adjusting guidelines, both in the Netherlands and abroad,” says Oudijk. 

Reference:

van der Windt, Larissa ISchaaf, Jelle M et al., Atosiban versus placebo for threatened preterm birth (APOSTEL 8): a multicentre, randomised controlled trial, The Lancet.

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Breast cancer death rates have stopped going down, reports research

A new paper in the Journal of Breast Imaging, published by Oxford University Press, indicates that breast cancer mortality rates have stopped declining in women older than age 74, and reconfirms that breast cancer mortality rates have stopped falling in women younger than age 40. This finding for older women is new.

Breast cancer is the second leading cause of cancer deaths in American women, with over 42,000 women dying of the disease in 2024. Before 1990, female breast cancer rates had been rising, and breast cancer mortality rates had been flat or increasing. Since 1990 there has been a steady decline in breast cancer mortality rates, which public health observers attribute both to the widespread use of mammograms and improvements in treatment.

The researchers, Debra Monticciolo and R. Edward Hendrick, assessed cancer mortality rates collected and maintained by the National Center for Health Statistics since 1990. For U.S. women overall breast cancer mortality rates have decreased steadily from 1990 to 2022, falling by 43.5% over that period. The most recent trend has been a decrease of 1.23% per year from 2010 to 2022, the lowest rate of decrease recorded since 1990. For U.S. women ages 20 to 39 (combining all races/ethnicities), breast cancer mortality rates decreased by 2.79% per year from 1990 until 2010, but have remained flat since 2010.

The investigation found that for women 75 years and older, the breast cancer mortality rate decreased by 1.26% per year from 1993 to 2013, when the rate stopped declining. For Asian, Hispanic, and Native American women (of all ages), breast cancer mortality rates have stopped declining over the most recent period: since 2009 for Asian women, since 2008 for Hispanic women, and since 2005 for Native American women.

Previous research indicated that breast cancer mortality rates stopped declining for women under 40 in 2010. The researchers here found that in both younger and older groups, the end of mortality rate decline was primarily due to mortality rates no longer declining for White women under 40 and over 74, as well as unfavorable trends for Hispanic women ages 20-39 years and for Asian, Hispanic, and Native American women 75 and older. Breast cancer mortality rates in Black women continued to decline in all age groups.

The investigators conducting this study contend that mortality rates have stopped declining for women under 40 and over 74 due to significant increases in stage IV breast cancers at diagnosis in these two age groups. Stage IV (metastatic) breast cancer at diagnosis has an extremely poor prognosis: a 31% 5-year survival rate.

This study indicates that increasing rates of advanced stage breast cancer at diagnosis is an important reason breast cancer mortality rates are no longer declining at the rate they once did. The researchers believe that this may be due to healthcare protocols. While the medical community currently recommends a breast cancer assessment for all women by age 25, breast cancer screening is only recommended for women under age 40 who are at higher-than-average risk. Some guidelines discourage women over 74 from screening.

Breast cancer mortality rate ratios for Black vs White women show the widest gap for women under age 40 years, suggesting that younger Black women are especially in need of alternatives to our current breast cancer risk assessment, screening, and treatment strategies, according to the authors.

“The fact that breast cancer mortality rates have stopped declining for women over age 74 is an alarming new trend,” said Monticciolo. “This is in addition to women under age 40 no longer seeing mortality rates decline from breast cancer. These groups are exactly those discouraged from breast cancer screening by some U.S. guidelines.”

Reference:

Debra Monticciolo,Recent Trends in Breast Cancer Mortality Rates for U.S. Women by Age and Race/Ethnicity, Journal of Breast Imaging, https://doi.org/10.1093/jbi/wbaf007.

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Hypothyroid patients with elevated inflammatory marker levels at elevated risk for MASLD: Study

A new study published in the journal of Nature Scientific Reports showed that the patients with hypothyroidism have increased risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD) when compared to those without hypothyroidism.

Lipid buildup in liver cells is a hallmark of non-alcoholic fatty liver disease (NAFLD). From basic hepatic steatosis to non-alcoholic steatohepatitis (NASH), which can lead to advanced fibrosis, cirrhosis, and eventually chronic liver failure, NAFLD includes a wide range of liver pathologies.

The term metabolic dysfunction-associated fatty liver disease (MASLD) has taken the role of NAFLD in recent years. The association between hypothyroidism and MASLD has been the subject of a significant number of observational research. However, the results are still unclear, with inconsistent findings from different investigations.

Thus, a sizable population cohort from the UK Biobank was used in the current study to methodically investigate the relationship between hypothyroidism and MASLD. To investigate the underlying possible processes and offer fresh population-based evidence for the influence of hypothyroidism on the risk of MASLD, further stratified, mediation, and nonlinear analyses were conducted.

A Cox proportional hazards model enhanced by several sensitivity analyses was used to examine the relationship between the incidence of hypothyroidism and the development of MASLD using prospective data from the UK Biobank. To evaluate possible effect modifiers, prognostic evaluations and stratified analyses were also carried out.

The study discovered that the probability of MASLD in patients with hypothyroidism was 1.711 times higher than that of individuals without hypothyroidism after properly controlling for a number of variables. A significantly higher risk of MASLD development was linked to both subtypes of hypothyroidism, namely surgical related hypothyroidism (SRH) and non-surgical related hypothyroidism (NSRH).

There is a 1.710-fold increase in risk for NSRH and a 1.763-fold increase for SRH. When it came to the risk of MASLD in people with NSRH, stratified analysis showed an interaction impact between gender and BMI. The importance of certain biomarkers in clarifying the connection between hypothyroidism and MASLD was demonstrated by mediation analysis. Also, this link was found to be significantly mediated by red cell distribution width, HbA1c, C-reactive protein, and total protein. Overall, people with hypothyroidism may be more susceptible to MASLD, especially if they have high levels of inflammatory markers.

Source:

Wang, H., Zheng, C., & Wang, P. (2025). Exploring the nexus between hypothyroidism and metabolic dysfunction-associated steatotic liver disease: a UK biobank cohort study. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-91221-7

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Court Restrains Medreich from Using Jubilant’s Losartan, Amlodipine, Citalopram Dossiers

Noida: In relief to Jubilant Generics Ltd, the Commercial Court No. II, Gautam Buddh Nagar, has granted a temporary injunction against Medreich Limited and three other defendants in a high-stakes intellectual property dispute concerning pharmaceutical product dossiers. The dispute centers around three key drugs, Losartan, Amlodipine, and Citalopram which Jubilant Generics alleges were unlawfully accessed and used for manufacturing in India in violation of its exclusive licensing agreements.

The order, delivered by Judge Kunal Vepa on February 25, 2025, restrains the defendants from using, reproducing, or sharing the copyright-protected product dossiers of Jubilant Generics and from manufacturing, distributing, or exporting the disputed pharmaceutical products.

The legal battle began when Jubilant Generics Ltd filed an original suit for permanent injunction on August 23, 2024, alleging that Medreich Limited and its co-defendants had illegally acquired and used confidential product dossiers belonging to the plaintiff. Jubilant argued that the unauthorized use of these dossiers amounted to copyright infringement, misappropriation of trade secrets, and breach of confidentiality agreements.

According to the plaintiff, the product dossiers in question pertained to three pharmaceutical formulations—Losartan, Amlodipine, and Citalopram—which had been developed by Jubilant Generics and licensed exclusively to Jamp Pharma Corporation, Canada, under a confidentiality and non-disclosure agreement (NDA) signed in 2010. The licensing agreement permitted Jamp Pharma to manufacture, distribute, and sell these drugs exclusively in Canada.

However, Jubilant alleged that Jamp Pharma unlawfully shared the product dossiers with Medreich Limited and three other Indian pharmaceutical companies, which then manufactured these drugs in India, in violation of the intellectual property rights of Jubilant Generics. The plaintiff contended that this constituted a breach of Section 51 of the Copyright Act, 1957.

After reviewing extensive arguments and documentation, the Commercial Court ruled in favor of Jubilant Generics, concluding that the plaintiff had established a prima facie case of copyright infringement. The court noted that Medreich Limited and the other defendants were not parties to the original licensing agreements and had no legal right to access or use Jubilant’s intellectual property. In its ruling, the court observed;

“Jamp Pharma was duty-bound to purchase the said products from the plaintiff for the Canadian market. However, the defendants, who were never privy to the original agreements, have unlawfully gained access to and used the product dossiers for manufacturing in India, which is a blatant infringement of the plaintiff’s copyright.”

Further emphasizing the importance of territorial restrictions, the court ruled;

“Jamp Pharma’s rights under the agreement were limited to Canada. The use of the plaintiff’s product dossiers by entities outside Canada for manufacturing, as admitted by defendant No. 4, is a clear breach of contract and intellectual property rights.”

Additionally, the court rejected the defendants’ claim that the agreements had expired and that Jamp Pharma had the right to share the product dossiers, stating;

“While the arbitration proceedings between Jubilant and Jamp Pharma are ongoing in Canada, the present suit concerns third-party defendants who were not part of the original agreements. Therefore, this matter is within the jurisdiction of this court.”

The court further noted that allowing the defendants to continue manufacturing the drugs in India would cause irreparable harm to Jubilant Generics, stating;

“The plaintiff’s right to protect their intellectual property shall prevail over the commercial interest of the defendants. The unauthorized use of the plaintiff’s product dossiers by the defendants has led to a loss of unique property, which cannot be compensated in monetary terms.”

Based on its findings, the Commercial Court issued a fresh temporary injunction, restraining the defendants from using, reproducing, or distributing the disputed product dossiers. It also barred them from manufacturing, distributing, or exporting the pharmaceutical products in question and sharing the confidential product dossiers with any third party. It held;

“In view of the above discussion, the answering defendants are hereby restrained from reproducing or using in any manner the copyrights protected product dossiers of the plaintiff in relation to the said products, and also for manufacturing, distributing and exporting the said products to any entity. The defendants are also restrained from sharing with any third party, or using directly or indirectly the plaintiff confidential information including the product dossiers in whole or in part for the said products.”

The court also ordered that the temporary injunction will remain in place until the final disposal of the case. The next hearing on related procedural matters is scheduled for April 9, 2025.

To view the original order, click on the link below:

https://medicaldialogues.in/pdf_upload/k8s0bu2ncd546liji4ve8jhmvs-277520.pdf

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Music therapy shows promise in reducing depression for dementia patients

A new review has found evidence that music-based therapy may benefit people living with dementia, particularly by improving symptoms of depression. The work has been published in Cochrane Database of Systematic Reviews.

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Researchers find no evidence that substituting NHS doctors with physician associates is necessarily safe

Researchers say they can find no convincing evidence that physician associates add value in UK primary care or that anesthetic associates add value in anesthetics, and some evidence suggests that they do not.

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At-home brain speed tests bridge cognitive data gaps

Online tests of women’s reaction times offer insights into cognitive function and could help fill data gaps on early cognitive problems, potentially shedding light on dementia development later in life, finds a new study led by researchers at UCL and other universities.

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Customized smartphone app shows promise in preventing further cognitive decline among older adults

A growing body of research indicates that older adults in assisted living facilities can delay or even prevent cognitive decline through interventions that combine multiple activities, such as improving diet, solving puzzles and increasing social interactions.

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