Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104521
Saghar Salehpour
<div><h3>Introduction</h3><div>PCOS affect 10-13% of women of reproductive age and it is the most common endocrine disorder of reproductive age. ASRM, ESHRE definition for PCOS is:</div><div>- oligo anovulation,</div><div>- clinical or biochemical hyperandrogenism,</div><div>- PCO in ultrasound.</div><div>Rotterdam criteria describe 4 phenotypes in PCOS.</div><div>Phenotype A: anovulation + hyperandrogenism + PCO in ultrasound (44.8%)</div><div>Phenotype B: hyperandrogenism + anovulation (14.9%)</div><div>Phenotype C: hyperandrogenism + PCO in ultrasound (16.2%)</div><div>Phenotype D: anovulation + PCO in ultrasound (19.5%)</div><div>There are 2 clinical subtypes for PCOS:</div><div>- <strong>Metabolic group</strong>: with higher BMI, higher glucose and insulin – More frequent in phenotype A, B, C.</div><div>- <strong>Reproductive group</strong>: lower BMI, lower insulin, higher IGF -1, higher LH, higher SHBG – More frequent in phenotype D.</div><div>According to 2023 PCOS guideline, AMH is considered as diagnostic criteria, but insulin resistance still not included in diagnostic criteria.</div></div><div><h3>Infertility treatment in PCOS</h3><div>One of difficult area of infertility treatment is PCOS. And in recent decades there is different approaches to improve the results. Some of these approaches are summaries here:</div><div>- The first step in treatment is life style modification, induction ovulation with SERM(Clomiphen citrate,…),Aromatase inhibitor, and Gonadotropins.</div><div>- In new literature, letrozole may become the first line of treatment, instead of clomiphen citrate.</div><div>- IVF,ICSI,IVM,Laparascopic ovarian drilling are other options for infertility treatment.</div><div>- Metformin is suggested to reduce OHSS, improve implantation and reduce miscarriage. But this drug is recommended in phenotype A, B, C.</div><div>- Other insulin sensitizer like Myoinositol and D chiro inositol, also can be used to ameliorate insulin resistance and decrease androgen level, and finally improve the result of ART cycles in PCOS.</div><div>- Vit D deficiency induce metabolic disorders and insulin resistance in PCOS and with vit D supplementation, we can have better result in infertility treatment of PCOS.</div><div>- Bariatric surgery is reserved for PCOS women who have BMI more than 35kg/m<sup>2</sup></div><div>In shahid Beheshti medical university, there was many researches on N-acetyl cysteine, Metformin, Myoinositol, chromium, L Carnitine as adjutant therapy in infertility treatment of PCOS patients.</div></div><div><h3>Complications of infertility treatment in PCOS</h3><div>- Clomiphene citrate resistance, more frequent in phenotype A.</div><div>- Endometrial hyperplasia, more frequent in phenotype A.</div><div>- OHSS, more likely in phenotype A.</div><div>- Thick endometrium on the day of trigger, more prevalent in phenotype D.</div></div><div><h3>Pregnancy outcomes after ART in PCOS</h3><div>- Lower live birth rate</div><div>- higher ra
{"title":"PCOS AND IT'S DIFFERENT ASPECTS IN INFERTILITY AND ART","authors":"Saghar Salehpour","doi":"10.1016/j.rbmo.2024.104521","DOIUrl":"10.1016/j.rbmo.2024.104521","url":null,"abstract":"<div><h3>Introduction</h3><div>PCOS affect 10-13% of women of reproductive age and it is the most common endocrine disorder of reproductive age. ASRM, ESHRE definition for PCOS is:</div><div>- oligo anovulation,</div><div>- clinical or biochemical hyperandrogenism,</div><div>- PCO in ultrasound.</div><div>Rotterdam criteria describe 4 phenotypes in PCOS.</div><div>Phenotype A: anovulation + hyperandrogenism + PCO in ultrasound (44.8%)</div><div>Phenotype B: hyperandrogenism + anovulation (14.9%)</div><div>Phenotype C: hyperandrogenism + PCO in ultrasound (16.2%)</div><div>Phenotype D: anovulation + PCO in ultrasound (19.5%)</div><div>There are 2 clinical subtypes for PCOS:</div><div>- <strong>Metabolic group</strong>: with higher BMI, higher glucose and insulin – More frequent in phenotype A, B, C.</div><div>- <strong>Reproductive group</strong>: lower BMI, lower insulin, higher IGF -1, higher LH, higher SHBG – More frequent in phenotype D.</div><div>According to 2023 PCOS guideline, AMH is considered as diagnostic criteria, but insulin resistance still not included in diagnostic criteria.</div></div><div><h3>Infertility treatment in PCOS</h3><div>One of difficult area of infertility treatment is PCOS. And in recent decades there is different approaches to improve the results. Some of these approaches are summaries here:</div><div>- The first step in treatment is life style modification, induction ovulation with SERM(Clomiphen citrate,…),Aromatase inhibitor, and Gonadotropins.</div><div>- In new literature, letrozole may become the first line of treatment, instead of clomiphen citrate.</div><div>- IVF,ICSI,IVM,Laparascopic ovarian drilling are other options for infertility treatment.</div><div>- Metformin is suggested to reduce OHSS, improve implantation and reduce miscarriage. But this drug is recommended in phenotype A, B, C.</div><div>- Other insulin sensitizer like Myoinositol and D chiro inositol, also can be used to ameliorate insulin resistance and decrease androgen level, and finally improve the result of ART cycles in PCOS.</div><div>- Vit D deficiency induce metabolic disorders and insulin resistance in PCOS and with vit D supplementation, we can have better result in infertility treatment of PCOS.</div><div>- Bariatric surgery is reserved for PCOS women who have BMI more than 35kg/m<sup>2</sup></div><div>In shahid Beheshti medical university, there was many researches on N-acetyl cysteine, Metformin, Myoinositol, chromium, L Carnitine as adjutant therapy in infertility treatment of PCOS patients.</div></div><div><h3>Complications of infertility treatment in PCOS</h3><div>- Clomiphene citrate resistance, more frequent in phenotype A.</div><div>- Endometrial hyperplasia, more frequent in phenotype A.</div><div>- OHSS, more likely in phenotype A.</div><div>- Thick endometrium on the day of trigger, more prevalent in phenotype D.</div></div><div><h3>Pregnancy outcomes after ART in PCOS</h3><div>- Lower live birth rate</div><div>- higher ra","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104521"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104524
Berk Emin Angün , Alper Eraslan , Türkan Gürsu
<div><h3>Objective</h3><div>To evaluate if DNA Fragmentation Index(DNA-FI) and high DNA stainability(HDS) effect fertilization rates in couples where the women are at young age and men are at advanced paternal age(1).</div></div><div><h3>Materials and methods</h3><div>This study was conducted in an international IVF Center in Kyrenia, Northern Cyprus, with retrospective data analysis of 103 IVF/ICSI cycles where embryos were of women <35years and men over 40years of age. The data was searched between January 2022 and July 2024. All procedures were routine standardized procedures performed in the center. The women with previous poor ovarian responses, low antral follicle counts (<7 follicles) and AMH levels below 1.1 ng/ml were excluded. Male partners who used any antioxidants or required intervention for obtaining sperms were not included. The age of woman and male partners were recorded. Sperm Chromatin Structure Assays with the results of total progressive sperm count, progressive sperm motility, Kruger morphology criteria, spermatozoa concentration, spermatozoa viability, live sperms with open acrosomes, total acrosome losses, DNA-FI and HDS levels were evaluated. Short antagonist protocols were used in all patients. M2 oocyte numbers, 2PNs and fertilization rates were analyzed. Fertilization rates were classified in three groups as rates below competency value (<65%), competent value (between 65%-80%) and over benchmark value (>80 %) according to Vienna Consensus(2). Kruger strict criteria were classified as <4 and equal or >4. DNA-FI levels were analyzed if there was any correlation with fertilization rates. The DNA-FI levels were classified into 5groups as; <15,15.1-20,20.1-25,25.1-30 and >30. The sperm high DNA stainability was classified into 4groups as; <7.5, 7.6-10, 10.1-15 and >15.1. The groups were compared in terms of fertilization rates.</div></div><div><h3>Results</h3><div>There were 103women in the study. The descriptive data were analyzed. There were no azoospermic men as individuals requiring interventions to obtain sperms were excluded from the study. 38.83%(n=40) of men had teratospermia, having less than 4%normal sperm morphology due to Kruger strict criteria. Among all men, 31%(n=32) had increased DNA-FI, but only 1.94%(n=2) of men had increased HDS. There was no significant correlation between DNA-FI levels and fertilization rates. There was no significant difference among DNA-FI levels or HDS levels with fertilization rate groups.</div></div><div><h3>Conclusion</h3><div>In our study there was no correlation between DNA-FI levels and fertility rates. The DNA-FI and HDS were not affecting fertilization rates in our study group. Couples of <35years old women and >40years of men were selected with sperm parameters including DNA-FI and HDS.Small number of patients is a limitation to our current study. Also, clinical pregnancy rates and live birth rates are missing but they will be included in
{"title":"DO DNA FRAGMENTATION INDEX AND HIGH DNA STAINABILITY HAVE ANY IMPACT ON FERTILIZATION RATES IN WOMEN UNDER 35 YEARS OF AGE HAVING MALE PARTNERS OVER 40 YEARS OF AGE, UNDERGOING IN VITRO FERTILIZATION AND INTRA CYTOPLASMIC INJECTION?","authors":"Berk Emin Angün , Alper Eraslan , Türkan Gürsu","doi":"10.1016/j.rbmo.2024.104524","DOIUrl":"10.1016/j.rbmo.2024.104524","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate if DNA Fragmentation Index(DNA-FI) and high DNA stainability(HDS) effect fertilization rates in couples where the women are at young age and men are at advanced paternal age(1).</div></div><div><h3>Materials and methods</h3><div>This study was conducted in an international IVF Center in Kyrenia, Northern Cyprus, with retrospective data analysis of 103 IVF/ICSI cycles where embryos were of women <35years and men over 40years of age. The data was searched between January 2022 and July 2024. All procedures were routine standardized procedures performed in the center. The women with previous poor ovarian responses, low antral follicle counts (<7 follicles) and AMH levels below 1.1 ng/ml were excluded. Male partners who used any antioxidants or required intervention for obtaining sperms were not included. The age of woman and male partners were recorded. Sperm Chromatin Structure Assays with the results of total progressive sperm count, progressive sperm motility, Kruger morphology criteria, spermatozoa concentration, spermatozoa viability, live sperms with open acrosomes, total acrosome losses, DNA-FI and HDS levels were evaluated. Short antagonist protocols were used in all patients. M2 oocyte numbers, 2PNs and fertilization rates were analyzed. Fertilization rates were classified in three groups as rates below competency value (<65%), competent value (between 65%-80%) and over benchmark value (>80 %) according to Vienna Consensus(2). Kruger strict criteria were classified as <4 and equal or >4. DNA-FI levels were analyzed if there was any correlation with fertilization rates. The DNA-FI levels were classified into 5groups as; <15,15.1-20,20.1-25,25.1-30 and >30. The sperm high DNA stainability was classified into 4groups as; <7.5, 7.6-10, 10.1-15 and >15.1. The groups were compared in terms of fertilization rates.</div></div><div><h3>Results</h3><div>There were 103women in the study. The descriptive data were analyzed. There were no azoospermic men as individuals requiring interventions to obtain sperms were excluded from the study. 38.83%(n=40) of men had teratospermia, having less than 4%normal sperm morphology due to Kruger strict criteria. Among all men, 31%(n=32) had increased DNA-FI, but only 1.94%(n=2) of men had increased HDS. There was no significant correlation between DNA-FI levels and fertilization rates. There was no significant difference among DNA-FI levels or HDS levels with fertilization rate groups.</div></div><div><h3>Conclusion</h3><div>In our study there was no correlation between DNA-FI levels and fertility rates. The DNA-FI and HDS were not affecting fertilization rates in our study group. Couples of <35years old women and >40years of men were selected with sperm parameters including DNA-FI and HDS.Small number of patients is a limitation to our current study. Also, clinical pregnancy rates and live birth rates are missing but they will be included in","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104524"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104593
Gokalp Oner , Cansu Oner , Noor Nabi Junejo
Objective
L-Carnitine, a pivotal compound present in mammals, is essential for the transport of long-chain fatty acids across the inner mitochondrial membrane. L-Carnitine is used for male infertility enhancing sperm parameters and it may serve as a protective mechanism against the overproduction of reactive oxygen species in the testis, which can damage sperm. This protective effect is accomplished by increasing the expression and activity of antioxidant enzymes as it demonstrates the ability to enhance sperm quality and overall fertility (1). However, the optimal and effective dosages for treatment has not been determined, yet.
In this retrospective multicentric study we aimed to find the effective dosages to improve the sperm parameters, embryo quality, and pregnancy rates of intracytoplasmic sperm injection (ICSI).
Materials and Methods
The ethic commitee approval was taken from Istanbul Aydin University (31-2024). 600 asthenoteratozoospermia men divided to 4 groups. Group1 is control, group 2 take 500 mg L-carnitine per daily before 3 months of ICSI attempt, group 3 take 1000 mg L-carnitine per daily before 3 months of ICSI attempt, group 4 take 2000 mg L-carnitine per daily before 3 months of ICSI attempt. There has been no female factor included in this study such as low ovarian reserve, advanced maternal aged, genetic problem, endometriosis, uterine anomalies, and hydrosalpinges.
Results
The clinical properties of the patients are summarized in Table 1. After carnitine usage, the sperm volume of the groups are similar. Sperm counts are significantly higher in group 3 and 4. Similarly sperm motility morphology are significantly increased in Group 3 and 4. Embryo quality is better in group2 and best in group 3 and 4 comparing the control. The chemical and clinical pregnancies are significantly high in group 4.
Discussion and conclusion
L-Carnitine demonstrates potential as a therapeutic intervention to enhance male fertility and mitigate sperm-related problems. There has been lots of study and different dosages found in these studied to improve sperm parameters (2). This multicentric study shows that 2000 mg L-carnitine levels is effective to enhance sperm parameters and get good quality embryos for assisted reproduction technology (ART). Additionaly, pregnancy rates are preferable if the L-carnitine has been begun before the assisted reproduction technology for asthenoteratozoospermia. Therefore, if there has been no female factor, L-carnitine may be started to men before ART attempts to improve sperm parameters, embryo quality, and pregnancy rates in ART.
{"title":"L-CARNITINE SUPPLEMENTATION BEFORE ASSISTED REPRODUCTION FOR MALE INFERTILITY","authors":"Gokalp Oner , Cansu Oner , Noor Nabi Junejo","doi":"10.1016/j.rbmo.2024.104593","DOIUrl":"10.1016/j.rbmo.2024.104593","url":null,"abstract":"<div><h3>Objective</h3><div>L-Carnitine, a pivotal compound present in mammals, is essential for the transport of long-chain fatty acids across the inner mitochondrial membrane. L-Carnitine is used for male infertility enhancing sperm parameters and it may serve as a protective mechanism against the overproduction of reactive oxygen species in the testis, which can damage sperm. This protective effect is accomplished by increasing the expression and activity of antioxidant enzymes as it demonstrates the ability to enhance sperm quality and overall fertility (1). However, the optimal and effective dosages for treatment has not been determined, yet.</div><div>In this retrospective multicentric study we aimed to find the effective dosages to improve the sperm parameters, embryo quality, and pregnancy rates of intracytoplasmic sperm injection (ICSI).</div></div><div><h3>Materials and Methods</h3><div>The ethic commitee approval was taken from Istanbul Aydin University (31-2024). 600 asthenoteratozoospermia men divided to 4 groups. Group1 is control, group 2 take 500 mg L-carnitine per daily before 3 months of ICSI attempt, group 3 take 1000 mg L-carnitine per daily before 3 months of ICSI attempt, group 4 take 2000 mg L-carnitine per daily before 3 months of ICSI attempt. There has been no female factor included in this study such as low ovarian reserve, advanced maternal aged, genetic problem, endometriosis, uterine anomalies, and hydrosalpinges.</div></div><div><h3>Results</h3><div>The clinical properties of the patients are summarized in Table 1. After carnitine usage, the sperm volume of the groups are similar. Sperm counts are significantly higher in group 3 and 4. Similarly sperm motility morphology are significantly increased in Group 3 and 4. Embryo quality is better in group2 and best in group 3 and 4 comparing the control. The chemical and clinical pregnancies are significantly high in group 4.</div></div><div><h3>Discussion and conclusion</h3><div>L-Carnitine demonstrates potential as a therapeutic intervention to enhance male fertility and mitigate sperm-related problems. There has been lots of study and different dosages found in these studied to improve sperm parameters (2). This multicentric study shows that 2000 mg L-carnitine levels is effective to enhance sperm parameters and get good quality embryos for assisted reproduction technology (ART). Additionaly, pregnancy rates are preferable if the L-carnitine has been begun before the assisted reproduction technology for asthenoteratozoospermia. Therefore, if there has been no female factor, L-carnitine may be started to men before ART attempts to improve sperm parameters, embryo quality, and pregnancy rates in ART.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104593"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Determining if serum LH levels on the hCG trigger day are correlated with live birth rates (LBR) following fresh embryo transfer with GnRH antagonist protocols.
Materials and Methods
A retrospective study was conducted at a university-based infertility clinic between January 2015 and December 2021. Participants were women aged 20-40 undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with fresh embryo transfer following a GnRH antagonist protocol. Women with normal basal FSH and TSH were included in the study. Exclusion criteria for the study were polycystic ovary syndrome (PCOS), poor responder status, recurrent abortions, and uterine abnormalities. Patients were categorized into two groups based on live birth (LB) and both groups were compared according to their age, antral follicle count (AFC), AMH, FSH, LH, progesterone, and estradiol levels, duration of stimulation, the dose of gonadotropins used, quality, and quantity of oocytes and embryos.
Results
Age, AFC, AMH, FSH, LH, and estradiol levels on D3, endometrial thickness on trigger day, total dose of gonadotropins used, duration of stimulation, starting day of antagonist administration, progesterone and estrogen levels on the hCG trigger day, follicles ≥14 mm and ≥17 mm on the trigger day, number of oocytes retrieved, number of MII oocytes, number of embryos and number of quality embryos were comparable in both groups. LH levels on the trigger day were the sole distinguishing characteristic between the two groups (Table 1).
Discussion and Conclusion
Our results revealed that elevated serum LH levels on the trigger day are linked to higher live births following fresh embryo transfer in GnRH antagonist cycles. It has been demonstrated in previous studies that LH plays a crucial role in various reproductive processes, including follicle development, ovulation, steroidogenesis, luteal function, and endometrial development (1,2). Our findings, which showed a significant discrepancy in LH levels on trigger day between the two groups suggest that elevated LH levels may contribute to higher implantation rates. Zhou et al. demonstrated in a large cohort that there is a positive association between serum LH levels on hCG trigger day and Iive birth rate after fresh embryo transfer in both normal ovarian responders and patients with PCOS (3). LH could serve as a predictive marker for determining whether to proceed with fresh embryo transfer in IVF cycles to optimize clinical outcomes.
{"title":"RELATIONSHIP BETWEEN SERUM LH LEVELS ON THE HCG TRIGGER DAY AND LIVE BIRTH RATES FOLLOWING FRESH EMBRYO TRANSFER WITH GNRH ANTAGONIST PROTOCOLS","authors":"Şeyma OSMANLIOĞLU , Koray Görkem Saçıntı , Bülent Berker","doi":"10.1016/j.rbmo.2024.104596","DOIUrl":"10.1016/j.rbmo.2024.104596","url":null,"abstract":"<div><h3>Objective</h3><div>Determining if serum LH levels on the hCG trigger day are correlated with live birth rates (LBR) following fresh embryo transfer with GnRH antagonist protocols.</div></div><div><h3>Materials and Methods</h3><div>A retrospective study was conducted at a university-based infertility clinic between January 2015 and December 2021. Participants were women aged 20-40 undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with fresh embryo transfer following a GnRH antagonist protocol. Women with normal basal FSH and TSH were included in the study. Exclusion criteria for the study were polycystic ovary syndrome (PCOS), poor responder status, recurrent abortions, and uterine abnormalities. Patients were categorized into two groups based on live birth (LB) and both groups were compared according to their age, antral follicle count (AFC), AMH, FSH, LH, progesterone, and estradiol levels, duration of stimulation, the dose of gonadotropins used, quality, and quantity of oocytes and embryos.</div></div><div><h3>Results</h3><div>Age, AFC, AMH, FSH, LH, and estradiol levels on D3, endometrial thickness on trigger day, total dose of gonadotropins used, duration of stimulation, starting day of antagonist administration, progesterone and estrogen levels on the hCG trigger day, follicles ≥14 mm and ≥17 mm on the trigger day, number of oocytes retrieved, number of MII oocytes, number of embryos and number of quality embryos were comparable in both groups. LH levels on the trigger day were the sole distinguishing characteristic between the two groups (Table 1).</div></div><div><h3>Discussion and Conclusion</h3><div>Our results revealed that elevated serum LH levels on the trigger day are linked to higher live births following fresh embryo transfer in GnRH antagonist cycles. It has been demonstrated in previous studies that LH plays a crucial role in various reproductive processes, including follicle development, ovulation, steroidogenesis, luteal function, and endometrial development (1,2). Our findings, which showed a significant discrepancy in LH levels on trigger day between the two groups suggest that elevated LH levels may contribute to higher implantation rates. Zhou et al. demonstrated in a large cohort that there is a positive association between serum LH levels on hCG trigger day and Iive birth rate after fresh embryo transfer in both normal ovarian responders and patients with PCOS (3). LH could serve as a predictive marker for determining whether to proceed with fresh embryo transfer in IVF cycles to optimize clinical outcomes.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104596"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104517
Serdar E Bulun MD
Adenomyosis and endometriosis are closely related disorders and originate from intracavitary endometrium. Oligoclones of endometrial glandular epithelial cells with somatic mutations (e.g., KRAS) and attached stromal cells may give rise to endometriosis if they travel to peritoneal surfaces or the ovary via retrograde menstruation or may be entrapped in the myometrium to give rise to adenomyosis. In both instances, the endometrial cell populations possess survival and growth capabilities conferred by somatic epithelial mutations. Stromal cell epigenetic abnormalities involve excessive local estrogen biosynthesis by aromatase and abnormal estrogen action via estrogen receptor-β, whereas aberrant progesterone receptor expression results in progesterone resistance in both endometriosis and adenomyosis. Endometriosis and adenomyosis have been treated successfully using GnRH analogues and aromatase inhibitors.
{"title":"ADENOMYOSIS: PATHOPHYSIOLOGY AND TREATMENT","authors":"Serdar E Bulun MD","doi":"10.1016/j.rbmo.2024.104517","DOIUrl":"10.1016/j.rbmo.2024.104517","url":null,"abstract":"<div><div>Adenomyosis and endometriosis are closely related disorders and originate from intracavitary endometrium. Oligoclones of endometrial glandular epithelial cells with somatic mutations (e.g., KRAS) and attached stromal cells may give rise to endometriosis if they travel to peritoneal surfaces or the ovary via retrograde menstruation or may be entrapped in the myometrium to give rise to adenomyosis. In both instances, the endometrial cell populations possess survival and growth capabilities conferred by somatic epithelial mutations. Stromal cell epigenetic abnormalities involve excessive local estrogen biosynthesis by aromatase and abnormal estrogen action via estrogen receptor-β, whereas aberrant progesterone receptor expression results in progesterone resistance in both endometriosis and adenomyosis. Endometriosis and adenomyosis have been treated successfully using GnRH analogues and aromatase inhibitors.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104517"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104590
Aycan Sıkı , Can Köse , Esin Kasap , Ebru Şahin Güleç , Ahmet Demir
Objective
Infertility is a condition that has been increasingly prevalent in recent years and has demographic, psychological, economic, and medical consequences in society. A review of the literature reveals a large number of studies conducted on azoospermia (AZO) and diminished ovarian reserve (DOR), but there are relatively few studies comparing these two conditions simultaneously. In our study, we aimed to contribute to the literature by comparing these two challenging groups that we treat in our clinic, both from the physician's and the patient's perspective.
Materials and Methods
In our study, patients diagnosed with azoospermia (AZO) and diminished ovarian reserve (DOR) who received intracytoplasmic sperm injection (ICSI) treatment at the Tepecik Training and Research Hospital, Department of Obstetrics and Gynecology, IVF Center, between January 1, 2017, and June 30, 2023, were examined. Within the inclusion and exclusion criteria, 100 cases were identified and divided into three groups based on treatment indications: AZO (n=34), DOR (n=34), and AZO+DOR (n=32). The patients' age, basal hormone levels (FSH, E2, PRG, AMH), treatment indications, embryo transfer days, and clinical pregnancy outcomes were documented.
Results
Clinical pregnancy rates were found to be 64.7% in the AZO group, 50% in the DOR group, and 34.4% in the DOR+AZO group. When the groups were compared among themselves, the clinical pregnancy rate in the AZO group was found to be significantly higher than in the DOR+AZO group (p=0.014). When comparing live birth rates among the groups, the live birth rate in the DOR+AZO group was found to be significantly lower than in the AZO group (p=0.022). When the types of pregnancies were examined among the groups, in the DOR group, pregnancies resulted in live births at a rate of 70.6% and in missed abortion at a rate of 29.4%.
Conclusions
Clinical pregnancy and live birth rates were found to be significantly higher in the AZO group compared to the DOR+AZO group. We believe that ovarian reserve in women is more determinant of IVF/ICSI success than sperm quality.
{"title":"EFFECT OF OVARIAN RESERVE ON PREGNANCY OUTCOMES IN PATIENTS UNDERGOING IVF TREATMENT DUE TO AZOOSPERMIA","authors":"Aycan Sıkı , Can Köse , Esin Kasap , Ebru Şahin Güleç , Ahmet Demir","doi":"10.1016/j.rbmo.2024.104590","DOIUrl":"10.1016/j.rbmo.2024.104590","url":null,"abstract":"<div><h3>Objective</h3><div>Infertility is a condition that has been increasingly prevalent in recent years and has demographic, psychological, economic, and medical consequences in society. A review of the literature reveals a large number of studies conducted on azoospermia (AZO) and diminished ovarian reserve (DOR), but there are relatively few studies comparing these two conditions simultaneously. In our study, we aimed to contribute to the literature by comparing these two challenging groups that we treat in our clinic, both from the physician's and the patient's perspective.</div></div><div><h3>Materials and Methods</h3><div>In our study, patients diagnosed with azoospermia (AZO) and diminished ovarian reserve (DOR) who received intracytoplasmic sperm injection (ICSI) treatment at the Tepecik Training and Research Hospital, Department of Obstetrics and Gynecology, IVF Center, between January 1, 2017, and June 30, 2023, were examined. Within the inclusion and exclusion criteria, 100 cases were identified and divided into three groups based on treatment indications: AZO (n=34), DOR (n=34), and AZO+DOR (n=32). The patients' age, basal hormone levels (FSH, E2, PRG, AMH), treatment indications, embryo transfer days, and clinical pregnancy outcomes were documented.</div></div><div><h3>Results</h3><div>Clinical pregnancy rates were found to be 64.7% in the AZO group, 50% in the DOR group, and 34.4% in the DOR+AZO group. When the groups were compared among themselves, the clinical pregnancy rate in the AZO group was found to be significantly higher than in the DOR+AZO group (p=0.014). When comparing live birth rates among the groups, the live birth rate in the DOR+AZO group was found to be significantly lower than in the AZO group (p=0.022). When the types of pregnancies were examined among the groups, in the DOR group, pregnancies resulted in live births at a rate of 70.6% and in missed abortion at a rate of 29.4%.</div></div><div><h3>Conclusions</h3><div>Clinical pregnancy and live birth rates were found to be significantly higher in the AZO group compared to the DOR+AZO group. We believe that ovarian reserve in women is more determinant of IVF/ICSI success than sperm quality.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104590"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104563
Ufuk ATLIHAN , Onur YAVUZ , Selcuk ERKILINC , Tevfik Berk BILDACI , Can ATA , Huseyin Aytug AVSAR
Objective
The aim of this study is to investigate the effects of levonorgestrel intrauterine device (LNG-IUD) use for contraception on dyspareunia and female sexual functions.
Materials and Methods
Our study included 96 women who applied to our gynecology outpatient clinic for routine check-ups and whose ultrasonographic findings were compatible with adenomyosis. Among these patients, LNG-IUD application was performed in 54 patients, and 42 patients did not accept the treatment. Among these patients, 54 patients underwent LNG-IUD application due to menometrorrhagia symptoms, and 42 patients did not accept the treatment. All patients were evaluated at a routine check-up 6 months after diagnosis, and all patients underwent Quality of Sexual Experience Scale (QSES), Female Sexual Function Index (FSFI), Visual Analog Scale (VAS) survey.
Results
No significant difference was detected between the average age and BMI averages of patients using LNG-IUD and patients not using LNG-IUD (p>0.05, p>0.05 respectively). There was no significant difference between the gravida and parity averages of patients using LNG-IUD and patients not using LNG-IUD (p>0.05, p>0.05 respectively). The VAS-dyspareunia score of patients using LNG-IUD was 3.88+0.64, and that of patients not using it was 4.36+0.72, and it was found to be significantly lower in the LNG group (p<0.026). The FSFI score of patients using LNG-IUD was 28.70+2.16, and that of patients not using it was 24.80+1.96, and it was found to be significantly higher in the LNG group (p<0.018). The QSES score of patients using LNG-IUD was 37.60+3.36, and that of patients not using it was 33.64+3.12, and it was found to be significantly higher in the LNG group (p<0.018).
Conclusion
We think that the use of LNG-IUD in the medical treatment of adenomyosis in the reproductive period will have a positive effect on female sexual functions, especially on dyspareunia.
{"title":"EFFECT OF LEVONORGESTREL IUD USE ON DYSPAREUNIA AND FEMALE SEXUAL FUNCTIONS IN PATIENTS WITH ADENOMYOSIS","authors":"Ufuk ATLIHAN , Onur YAVUZ , Selcuk ERKILINC , Tevfik Berk BILDACI , Can ATA , Huseyin Aytug AVSAR","doi":"10.1016/j.rbmo.2024.104563","DOIUrl":"10.1016/j.rbmo.2024.104563","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study is to investigate the effects of levonorgestrel intrauterine device (LNG-IUD) use for contraception on dyspareunia and female sexual functions.</div></div><div><h3>Materials and Methods</h3><div>Our study included 96 women who applied to our gynecology outpatient clinic for routine check-ups and whose ultrasonographic findings were compatible with adenomyosis. Among these patients, LNG-IUD application was performed in 54 patients, and 42 patients did not accept the treatment. Among these patients, 54 patients underwent LNG-IUD application due to menometrorrhagia symptoms, and 42 patients did not accept the treatment. All patients were evaluated at a routine check-up 6 months after diagnosis, and all patients underwent Quality of Sexual Experience Scale (QSES), Female Sexual Function Index (FSFI), Visual Analog Scale (VAS) survey.</div></div><div><h3>Results</h3><div>No significant difference was detected between the average age and BMI averages of patients using LNG-IUD and patients not using LNG-IUD (p>0.05, p>0.05 respectively). There was no significant difference between the gravida and parity averages of patients using LNG-IUD and patients not using LNG-IUD (p>0.05, p>0.05 respectively). The VAS-dyspareunia score of patients using LNG-IUD was 3.88+0.64, and that of patients not using it was 4.36+0.72, and it was found to be significantly lower in the LNG group (p<0.026). The FSFI score of patients using LNG-IUD was 28.70+2.16, and that of patients not using it was 24.80+1.96, and it was found to be significantly higher in the LNG group (p<0.018). The QSES score of patients using LNG-IUD was 37.60+3.36, and that of patients not using it was 33.64+3.12, and it was found to be significantly higher in the LNG group (p<0.018).</div></div><div><h3>Conclusion</h3><div>We think that the use of LNG-IUD in the medical treatment of adenomyosis in the reproductive period will have a positive effect on female sexual functions, especially on dyspareunia.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104563"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104512
Michel Abou Abdallah
Ovarian reserve tests started to emerge during the rise of ART in the late 1980s to predict both responsiveness to superovulation drugs and the odds of pregnancy with treatment. They include both biochemical basal and provocative tests and ultrasound imaging of the ovaries.
Most of these measures, however, have poor predictive value, often because they are indirect measures of ovarian reserve or have substantial intracycle or intercycle variability.
The purpose of using ovarian reserve testing as a screening test is to identify infertility patients at risk for DOR, who are more likely to have poor response to gonadotropin stimulation and less likely to achieve pregnancy with ART or ovulation induction.
The ideal ovarian reserve test should be affordable, noninvasive, and rapidly interpretable
It should be able to detect the decline in ovarian reserve at an early enough stage such that timely interventions could be pursued if desired. Lastly, it should have validity, ie, good sensitivity and specificity.
Optimizing specificity sacrifices sensitivity and the ability to identify all women with DOR.
Ovarian reserve tests have limitations and should not be used as sole criteria to deny patients access to ARTor other treatments.
Evidence of DOR does not necessarily mean inability to conceive, only that it may be less likely.
Finally, ovarian reserve testing may be considered as a screening tool in selected populations of women for assisting in their reproductive life planning.
While there is currently no perfect ovarian reserve test, both AFC and AMH level have good predictive value and are superior to day-3 FSH.
{"title":"IS OVERIAN RESERVE A GUIDE TO OVARIAN STIMULATION","authors":"Michel Abou Abdallah","doi":"10.1016/j.rbmo.2024.104512","DOIUrl":"10.1016/j.rbmo.2024.104512","url":null,"abstract":"<div><div>Ovarian reserve tests started to emerge during the rise of ART in the late 1980s to predict both responsiveness to superovulation drugs and the odds of pregnancy with treatment. They include both biochemical basal and provocative tests and ultrasound imaging of the ovaries.</div><div>Most of these measures, however, have poor predictive value, often because they are indirect measures of ovarian reserve or have substantial intracycle or intercycle variability.</div><div>The purpose of using ovarian reserve testing as a screening test is to identify infertility patients at risk for DOR, who are more likely to have poor response to gonadotropin stimulation and less likely to achieve pregnancy with ART or ovulation induction.</div><div>The ideal ovarian reserve test should be affordable, noninvasive, and rapidly interpretable</div><div>It should be able to detect the decline in ovarian reserve at an early enough stage such that timely interventions could be pursued if desired. Lastly, it should have validity, ie, good sensitivity and specificity.</div><div>Optimizing specificity sacrifices sensitivity and the ability to identify all women with DOR.</div><div>Ovarian reserve tests have limitations and should not be used as sole criteria to deny patients access to ARTor other treatments.</div><div>Evidence of DOR does not necessarily mean inability to conceive, only that it may be less likely.</div><div>Finally, ovarian reserve testing may be considered as a screening tool in selected populations of women for assisting in their reproductive life planning.</div><div>While there is currently no perfect ovarian reserve test, both AFC and AMH level have good predictive value and are superior to day-3 FSH.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104512"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Objective</h3><div>Carbon tetrachloride (CCl4) is frequently used in animal research to generate hepatotoxicity due to the causes oxidative stress within the organism. Lavandula Angustifolia is well-known for its antioxidant capabilities, which can aid in the prevention and treatment of future hepatotoxicity. Medical ozone therapy is the appropriate dosage of ozone gas. Medical ozone's ability to reduce oxidative stress suggests that it could be used to prevent and treat hepatotoxicity. The aim of this study was to investigate the effect of Lavandula, medical ozone and Lavandula+medical ozone treatments on the sperm counts and sperm morphology of the rat which have hepatotoxicity.</div></div><div><h3>Materials and methods</h3><div>The male Wistar rats chosen in the study were 8-12 weeks old and weighed 250-500 g with seven animals in each group, four groups were created as control, lavandula, medical ozone and lavandula and medical ozone. For ten days, 0.2 ml/kg of CCl4 was intraperitoneally injected into each of the 28 rats in these four groups. Following CCl4 delivery, a group other than the control group received 400 mg/kg Lavandula angustifolia oil via gavage every other day for 14 days. An intraperitoneal injection of 1 mg/kg medical ozone was given for 7 cycles to a different group. For seven cycles, the final experimental group received both 1 mg/kg of medical ozone intraperitoneally and 400 mg/kg of Lavandula angustifolia oil by gavage. Extracted sperm samples from epididymis incubated in PBS for ten minutes at 37 °C. Spermac Kit was used to stain the smeared and fixed sperm samples. The sample was counted in ten fields using a Makler camera and a light microscope with 40X objective. Ethics certificate from Maltepe University Animal Experiments Local Ethics Committee was obtained for this study (No: 2023.06.03).</div></div><div><h3>Results</h3><div>It was determined that, in comparison to the control group and Lavandula enhanced the sperm count (p<0.001) when added to the treatment protocol for the rats with liver damage, both in combination and independently from medical ozone. But when combined with medical ozone, lavandula was found to have no effect on sperm count when compared to the control group (p>0.05). However, there is a variation in the overall number of head, neck, and tail anomalies across the three groups when analyzing the sperm morphology in terms of abnormalities. In other words, there is a difference in Lavandula, medical ozone and both groups (p<0.001). But there was no difference (p>0.05) between the control group and the other groups.</div></div><div><h3>Conclusions</h3><div>According to our obtained results, although there was no statistically significant increase in the sperm counts of rats treated with medical ozone and Lavandula+ medical ozone, the increase in sperm counts was observed only in rats treated with Lavandula, suggesting that medical ozone may suppress the effect of Lavandula. Our
{"title":"THE EFFECTS OF LAVANDULA AND MEDICAL OZONE THERAPY ON SPERMIOGRAM PARAMETERS IN RATS WITH LIVER DAMAGE INDUCED BY CARBON TETRACHLORIDE","authors":"Nergis Özlem KILIÇ , İrem Zehra TAŞ , Erisa ACAR , Arife Dilşad AKDAĞ , Çağrı ÖNER , Necdet ALTINER","doi":"10.1016/j.rbmo.2024.104585","DOIUrl":"10.1016/j.rbmo.2024.104585","url":null,"abstract":"<div><h3>Objective</h3><div>Carbon tetrachloride (CCl4) is frequently used in animal research to generate hepatotoxicity due to the causes oxidative stress within the organism. Lavandula Angustifolia is well-known for its antioxidant capabilities, which can aid in the prevention and treatment of future hepatotoxicity. Medical ozone therapy is the appropriate dosage of ozone gas. Medical ozone's ability to reduce oxidative stress suggests that it could be used to prevent and treat hepatotoxicity. The aim of this study was to investigate the effect of Lavandula, medical ozone and Lavandula+medical ozone treatments on the sperm counts and sperm morphology of the rat which have hepatotoxicity.</div></div><div><h3>Materials and methods</h3><div>The male Wistar rats chosen in the study were 8-12 weeks old and weighed 250-500 g with seven animals in each group, four groups were created as control, lavandula, medical ozone and lavandula and medical ozone. For ten days, 0.2 ml/kg of CCl4 was intraperitoneally injected into each of the 28 rats in these four groups. Following CCl4 delivery, a group other than the control group received 400 mg/kg Lavandula angustifolia oil via gavage every other day for 14 days. An intraperitoneal injection of 1 mg/kg medical ozone was given for 7 cycles to a different group. For seven cycles, the final experimental group received both 1 mg/kg of medical ozone intraperitoneally and 400 mg/kg of Lavandula angustifolia oil by gavage. Extracted sperm samples from epididymis incubated in PBS for ten minutes at 37 °C. Spermac Kit was used to stain the smeared and fixed sperm samples. The sample was counted in ten fields using a Makler camera and a light microscope with 40X objective. Ethics certificate from Maltepe University Animal Experiments Local Ethics Committee was obtained for this study (No: 2023.06.03).</div></div><div><h3>Results</h3><div>It was determined that, in comparison to the control group and Lavandula enhanced the sperm count (p<0.001) when added to the treatment protocol for the rats with liver damage, both in combination and independently from medical ozone. But when combined with medical ozone, lavandula was found to have no effect on sperm count when compared to the control group (p>0.05). However, there is a variation in the overall number of head, neck, and tail anomalies across the three groups when analyzing the sperm morphology in terms of abnormalities. In other words, there is a difference in Lavandula, medical ozone and both groups (p<0.001). But there was no difference (p>0.05) between the control group and the other groups.</div></div><div><h3>Conclusions</h3><div>According to our obtained results, although there was no statistically significant increase in the sperm counts of rats treated with medical ozone and Lavandula+ medical ozone, the increase in sperm counts was observed only in rats treated with Lavandula, suggesting that medical ozone may suppress the effect of Lavandula. Our","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104585"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.rbmo.2024.104582
Melike Ucak , Kerem Dalgic , Begum Durkut , Hana Asghari , Mert Turgal , Ozgur Oktem , Ciler Celik-Ozenci
<div><h3>Objective</h3><div>Placenta is essential for coordinating the maternal response to pregnancy and releases molecules that affect maternal physiology. Placenta organoids offer a novel model for studying placental development and function, enabling researchers to explore interactions among the placenta's cell types. Exosomes, 30-150 nm extracellular vesicles formed via the endosomal pathway, transport signaling molecules and regulate cellular functions. Syncytiotrophoblast is the main source of placenta-derived extracellular vesicles. While exosome profiles of various tissue organoid models are documented, data on human placenta organoids (HPO) is lacking. This study aims to investigate if the exosome profile of HPOs can mimic that of <em>in vivo</em> human placenta.</div></div><div><h3>Materials and Methods</h3><div>In our study, with consent obtained from patients at the Obstetrics and Gynecology Clinic of Koç University Hospital, CTB isolation was performed from surgically obtained material of 6-9 weeks healthy pregnancy elective terminations (curettage), and HPO created by embedding the CTB cells in Matrigel. HPOs cultured at 37°C in a 5% CO2 environment with trophoblast organoid medium (TOM). HPOs were characterized using immunofluorescence with antibodies labeled with anti-Ki67, anti-CYT7, and anti-bHCG. TOM-conditioned medium was collected on days3 and 5 of the organoid culture. An explant culture (ExC) was established from the same villi used for HPO production and its conditioned media were collected at 24h and 48h. Exosomes were isolated using ultracentrifugation (100,000g for 2h). Exosome characterization involved size and concentration analysis using Nanoparticle Tracking Analysis (NTA) and detection of CD63 protein, an exosome-specific surface marker, using Western Blot.</div></div><div><h3>Results</h3><div>In HPOs, CTB cells located in the outer part of the organoids were specifically marked by the nuclear expression of the proliferation marker Ki67 and the cytoplasmic expression of CYT7. Additionally, STB cells in the inner part of the placenta organoid were specifically identified by bHCG labeling. The NTA results of HPOs and ExC revealed distinct particle concentrations over time. For HPO, the particle concentration (particles/ml) was 1.71 × 10<sup>10</sup>±9.32 × 10<sup>8</sup> on day3 and 7.39 × 10<sup>10</sup>±1.37 × 10<sup>10</sup> by day5. In comparison, explant cell culture showed a particle concentration (particles/ml) of 4.73 × 10<sup>10</sup>±5.11 × 10<sup>9</sup> at 24h and 8.69 × 10<sup>9</sup>±2.55 × 10<sup>8</sup> at 48h. CD63 protein expression confirmed the successful isolation of exosomes from HPO and ExC.</div></div><div><h3>Conclusion</h3><div>This research provides the first evidence of exosomes released from HPOs, showing that these organoids can functionally mimic the <em>in vivo</em> placenta. This finding is crucial for future studies, suggesting that HPOs could be used in drug trials and for comparin
{"title":"NOVEL FINDINGS OF EXOSOMES IN HUMAN PLACENTA ORGANOIDS","authors":"Melike Ucak , Kerem Dalgic , Begum Durkut , Hana Asghari , Mert Turgal , Ozgur Oktem , Ciler Celik-Ozenci","doi":"10.1016/j.rbmo.2024.104582","DOIUrl":"10.1016/j.rbmo.2024.104582","url":null,"abstract":"<div><h3>Objective</h3><div>Placenta is essential for coordinating the maternal response to pregnancy and releases molecules that affect maternal physiology. Placenta organoids offer a novel model for studying placental development and function, enabling researchers to explore interactions among the placenta's cell types. Exosomes, 30-150 nm extracellular vesicles formed via the endosomal pathway, transport signaling molecules and regulate cellular functions. Syncytiotrophoblast is the main source of placenta-derived extracellular vesicles. While exosome profiles of various tissue organoid models are documented, data on human placenta organoids (HPO) is lacking. This study aims to investigate if the exosome profile of HPOs can mimic that of <em>in vivo</em> human placenta.</div></div><div><h3>Materials and Methods</h3><div>In our study, with consent obtained from patients at the Obstetrics and Gynecology Clinic of Koç University Hospital, CTB isolation was performed from surgically obtained material of 6-9 weeks healthy pregnancy elective terminations (curettage), and HPO created by embedding the CTB cells in Matrigel. HPOs cultured at 37°C in a 5% CO2 environment with trophoblast organoid medium (TOM). HPOs were characterized using immunofluorescence with antibodies labeled with anti-Ki67, anti-CYT7, and anti-bHCG. TOM-conditioned medium was collected on days3 and 5 of the organoid culture. An explant culture (ExC) was established from the same villi used for HPO production and its conditioned media were collected at 24h and 48h. Exosomes were isolated using ultracentrifugation (100,000g for 2h). Exosome characterization involved size and concentration analysis using Nanoparticle Tracking Analysis (NTA) and detection of CD63 protein, an exosome-specific surface marker, using Western Blot.</div></div><div><h3>Results</h3><div>In HPOs, CTB cells located in the outer part of the organoids were specifically marked by the nuclear expression of the proliferation marker Ki67 and the cytoplasmic expression of CYT7. Additionally, STB cells in the inner part of the placenta organoid were specifically identified by bHCG labeling. The NTA results of HPOs and ExC revealed distinct particle concentrations over time. For HPO, the particle concentration (particles/ml) was 1.71 × 10<sup>10</sup>±9.32 × 10<sup>8</sup> on day3 and 7.39 × 10<sup>10</sup>±1.37 × 10<sup>10</sup> by day5. In comparison, explant cell culture showed a particle concentration (particles/ml) of 4.73 × 10<sup>10</sup>±5.11 × 10<sup>9</sup> at 24h and 8.69 × 10<sup>9</sup>±2.55 × 10<sup>8</sup> at 48h. CD63 protein expression confirmed the successful isolation of exosomes from HPO and ExC.</div></div><div><h3>Conclusion</h3><div>This research provides the first evidence of exosomes released from HPOs, showing that these organoids can functionally mimic the <em>in vivo</em> placenta. This finding is crucial for future studies, suggesting that HPOs could be used in drug trials and for comparin","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 ","pages":"Article 104582"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143141347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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