OBJECTIVE: To compare two cancellation policies in controlled ovarian stimulation-intrauterine insemination (COS-IUI) cycles to lower the risk of multiple pregnancies (MP). DESIGN: We performed a bicentric retrospective cohort study in two academic medical centers: Angers (group A) and Besançon (group B) University Hospitals. We included 7056 COS-IUI cycles between 2011 and 2019. In group A, cancellation strategy was based on an algorithm taking into account the woman's age, the serum estradiol level, and the number of follicles of 14 mm or greater on ovulation trigger day. In group B, cancellation strategy was case-by-case and physician-dependent, based on the woman's age, number of follicles of 15 mm or greater, and the previous number of failed COS-IUI cycles, without any predefined cut-off. Our main outcome measures were the MP rate (MPR) and the live-birth rate (LBR). RESULTS: We included 884 clinical pregnancies (790 singletons, 86 twins, and 8 triplets) obtained from 6582 COS-IUI cycles. MPR was significantly lower in group A compared with group B (8.1% vs 13.3%, P = 0.01), but LBR were comparable (10.8% vs 11.8%, P = 0.19). Multivariate logistic regression found the following to be risk factors for MP: the "cancellation strategy" effect (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.02-2.60) and the number of follicles of 14 mm or greater (aOR 1.39, 95% CI 1.16-1.66). Cycle cancellation rate for excessive response was significantly lower in group A compared with group B (1.3% vs 2.4%, P < 0.001). CONCLUSIONS: The use of an algorithm based on the woman's age, serum estradiol level and number of follicles of at least 14 mm on trigger day allows the MPR to be reduced without impacting the LBR.
BACKGROUND: In 15-49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15-49 years-old men diagnosed with TC or L in 2018. We designed a national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15-49 years-old men diagnosed with TC or L who banked sperm. RESULTS: Among 15-49 years-old men, INCa estimated 38,048 new cancer diagnoses in metropolitan France in 2018: 2,630 TC and 3,913 L (943 HL and 2,970 NHL). The CECOS network provided data from 26/27 metropolitan centers (96% response rate): 1,079 sperm banking for men with TC, 375 for HL and 211 for NHL. We estimated that the 2018 sperm banking rate in France was 41% for TC, 40% for HL, and 7% for NHL. CONCLUSIONS: To our knowledge, our paper is the first cross-sectional study with multicenter and national data analyzing FP rate in cancer men: it suggests an efficient pathway for men to FP before cancer treatment, compared to previously published studies. Although sperm banking rate in 15-49 years-old men could definitely be improved, further studies should evaluate the information given to patients before gonadotoxic treatments, the factors associated with the absence of sperm banking and whether this lack of referral induces a loss of chance for these men.
RéSUMé: CONTEXTE: Chez les hommes de 15 à 49 ans, les principaux cancers sont le cancer du testicule (CT) et les lymhomes (L): la congélation de spermatozoïdes éjaculés est utilisée en première intention pour leur préservation de fertilité (PF) avant traitement du cancer. Notre objectif était d'analyser le taux de PF chez les hommes de 15 à 49 ans diagnostiqués avec un CT ou un L en 2018 en France. Nous avons réalisé une étude nationale transversale descriptive du taux de congelation de spermatozoïdes chez les hommes âgés de 15 à 49 ans diagnostiqués avec un CT, un L de Hodgkin (LH) ou un L non-Hodgkinien (LNH). A partir des données de l'Institut National du Cancer (INCa) de 2018, nous avons extrait l'incidence estimée de CT et de L en France métropolitaine. A partir des données du bilan d'activité 2018 de la Federation Française des CECOS (Centre d'Etude et de Conservation des Oeufs et du Sperme), nous avons extrait le nombre d'hommes avec un CT ou un L qui ont congelé leurs spermatozoïdes. Nous avons enfin estimé la proportion d'hommes de 15 à 49 ans diagnostiqués avec un CT ou un L qui ont congelé leurs spermatozoïdes. RéSULTATS: Chez les hommes de 15 à 49 ans, l'INCa a estimé en 2018 38 048 nouveaux cas de cancers diagnostiqués en France métropolitaine en 2018: 2 630 CT et 3 913 L (943 LH et 2 970 LNH). Le réseau des CECOS a produit les résultats issus de 26/27 centres métropolitains (taux de réponse de 96%): 1 079 congélations de sperme pour des hommes atteints de CT, 375 pour LH et 211 pour LNH. Nous avons estimé que le taux de congelation de spermatozoïdes de 2018 en France était de 41% pour le CT, 40% pour le LH et 7% pour le LNH. CONCLUSIONS: A notre connaissance, notre travail est la première étude transversale multicentrique de données nationales analysant le taux de PF chez les hommes atteints de cancer: il suggère un parcours patient efficace pour la PF des hommes avant traitement d'un cancer, par rapport aux études précédemment publiées. Bien que le taux de PF chez les hommes puisse certainemen être amélioré, des études futures devraient évaluer l'information donnée aux patients avant traitement gonadotoxique, les facteurs associés à l'absence de PF et si le défaut d'adressage au CECOS induit un perte de chance pour ces hommes. MOTS-CLéS: Chimiothérapie, Radiothérapie, Oncofertiité, Azoospermia, Paternité.
There is great controversy as to whether women with Diminished Ovarian Reserve (DOR) exhibit only a quantitative decrease in ovarian reserve or also impaired oocyte and embryo quality. In this retrospective study, we aimed to evaluate the impact of DOR on embryo morphokinetic parameters with a time-lapse system. 1314 embryos were obtained from 256 couples undergoing IVF or ICSI cycles, with 242 embryos in the DOR group as classified by the Bologna and POSEIDON criteria and 1072 embryos derived from the Normal Ovarian Reserve (NOR) group. For each morphokinetic parameter (t2, t3, t4, t5, t8, tB, ECC2, cc2a, ECC3, s2, s3), a generalized linear mixed model was created to control for female age, BMI, smoking status, method of insemination and correlation between oocytes from a same cohort. No significant association was found between DOR and any of the morphokinetic parameters studied. In a secondary analysis, we evaluated the influence of maternal aging, comparing morphokinetic characteristics between two age groups (<37 and ≥37 years). In the univariate analysis, we found that embryos from older women displayed a slower embryo development (in particular for t3, t4, t5, tB, and ECC2), although without statistical significance in the multivariate analysis. In conclusion, our study did not reveal any substantial impact of ovarian aging on early morphokinetic parameters and suggested potential biases that may be a source of controversy in the literature.
Male infertility has increased in the last decade. Pathophysiologic mechanisms behind extreme oligospermia (EO) are not yet fully understood. In new "omics" approaches, metabolomic can offer new information and help elucidate these mechanisms. We performed a metabolomics study of the seminal fluid (SF) in order to understand the mechanisms implicated in EO. We realized a targeted quantitative analysis using high performance liquid chromatography and mass spectrometry to compare the SF metabolomic profile of 19 men with EO with that of 22 men with a history of vasectomy (V) and 20 men with normal semen parameters (C). A total of 114 metabolites were identified. We obtained a multivariate OPLS-DA model discriminating the three groups. Signatures show significantly higher levels of amino acids and polyamines in C group. The sum of polyunsaturated fatty acids and free carnitine progressively decrease between the three groups (C > EO > V) and sphingomyelins are significantly lower in V group. Our signature characterizing EO includes metabolites already linked to infertility in previous studies. The similarities between the signatures of the EO and V groups are clear evidence of epididymal dysfunction in the case of testicular damage. This study shows the complexity of the metabolomic dysfunction occurring in the SF of EO men and underlines the importance of metabolomics in understanding male infertility.
The objective was to assess whether the measurement of serum estradiol (E2) level on trigger day in controlled ovarian stimulation with intrauterine insemination (COS-IUI) cycles helps lower the multiple pregnancy (MP) rate. We performed a unicentric observational study. We included all patients who underwent COS-IUI and had a subsequent clinical pregnancy (CP) between 2011 and 2019. Our main outcome measure was the area under Receiver-Operating Characteristic (ROC) curve. We included 455 clinical pregnancies (CP) obtained from 3387 COS-IUI cycles: 418 singletons, 35 twins, and 2 triplets. The CP, MP, and live birth rates were respectively 13.4%, 8.1% and 10.8%. The area under ROC curve for peak serum E2 was 0.60 (0.52-0.69). The mean E2 level was comparable between singletons and MP (260.1 ± 156.1 pg/mL vs. 293.0 ± 133.4 pg/mL, p = 0.21, respectively). Univariate and multivariate logistic regression analysis showed that E2 level was not predictive of MP rate (aOR: 1.13 (0.93-1.37) and 1.06 (0.85-1.32), respectively). Our study shows that, when strict cancelation criteria based on the woman's age and follicular response on ultrasound are applied, the measurement of peak serum E2 levels does not help reduce the risk of MP in COS-IUI cycles.
Estradiol , Ovulation Induction , Pregnancy , Female , Humans , Pregnancy, Multiple , Gonadotropins , Pregnancy Rate , Insemination , Insemination, Artificial , Retrospective Studies
Time-lapse systems (TLS) and associated algorithms are interesting tools to improve embryo selection. This study aimed to evaluate how TLS and KIDScore™ algorithm changed our practices of embryo selection, as compared to a conventional morphological evaluation, and improved clinical pregnancy rates (CPR). In the study group (year 2020, n = 303 transfers), embryos were cultured in an EmbryoScope+ time-lapse incubator. A first team observed embryos conventionally once a day, while a second team selected the embryos for transfer based on time-lapse recordings. In the control group (year 2019, n = 279 transfers), embryos were selected using the conventional method, and CPR were recorded. In 2020, disagreement between TLS and the conventional method occurred in 32.1% of transfers, more often for early embryos (34.7%) than for blastocysts (20.5%). Irregular morphokinetic events (direct or reverse cleavage, multinucleation, abnormal pronuclei) were detected in 54.9% of the discordant embryos. When it was available, KIDScore™ was decreased for 73.2% of the deselected embryos. Discordant blastocysts mainly corresponded with a decrease in KIDScore™ (90.9%), whereas discordant Day 3 embryos resulted from a decreased KIDScore™ and/or an irregular morphokinetic event. CPR was significantly improved in the TLS group (2020), as compared to the conventional group (2019) (32.3% vs. 21.9%, p = 0.005), even after multivariate analysis. In conclusion, TLS is useful to highlight some embryo development abnormalities and identify embryos with the highest potential for pregnancy.
BACKGROUND: Many studies reported that reproductive desire could be high among transgender individuals. In France, fertility preservation and sperm donation were very little proposed to transgender individuals until recently, mainly because the Bioethics Law allows the use of assisted reproductive technologies only in infertile couples and prohibits surrogacy. OBJECTIVES: To evaluate the distribution of care on the French territory concerning fertility preservation and sperm donation in transgender individuals. MATERIALS AND METHODS: A multicentric national survey was carried out between January 2019 and October 2020 in 28 assisted reproductive technology centres of the French CECOS (Centres d'Etudes et de Conservation des Oeufs et du Sperme) network. Each centre was questioned to find out how many transgender individuals came, were informed and cared for fertility preservation and sperm donation. RESULTS: Concerning fertility preservation, 71.4% of centres received transgender individuals and performed gamete cryopreservation; 581 transgender individuals consulted for fertility preservation. Transgender women were more likely to desire (p < 0.0001) and achieve (p < 0.0001) fertility preservation than transgender men. Concerning sperm donation in couples including a transgender man, 68% of centres offer the complete course from the first consultation to the completion of the assisted reproductive technology cycles; 122 offsprings have been conceived with sperm donation in couples including a transgender man since 1999. DISCUSSION: Our results showed that even if all centres do not propose fertility preservation or sperm donation in transgender individuals, these assisted reproductive technologies are present throughout the French territory. The major point is that both fertility preservation and sperm donation in transgender individuals have grown significantly and that the care of these patients is improving year after year. CONCLUSION: In France, most of CECOS centres can take care of transgender individuals for fertility preservation and sperm donation. The French Bioethics Law allows these latter, and transgender individuals can benefit from a financial support of the national health care insurance for fertility preservation and sperm donation.
Fertility Preservation/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Reproductive Techniques, Assisted/statistics & numerical data , Sperm Retrieval/statistics & numerical data , Transsexualism/therapy , Adult , Female , France , Health Services for Transgender Persons/statistics & numerical data , Humans , Male
INTRODUCTION: Serum oestradiol concentration at the time of frozen embryo transfer (FET) in artificial cycle are lower when using transdermal administration of oestrogen for endometrial preparation compared to the vaginal route. This difference could have consequences for placentation and establishment of maternal-foetal circulation. The aim of our study was to compare the birth weight of newborns and the perinatal issues after FET in an artificial cycle with regard to the route of administration of oestrogens. METHODS: Retrospective monocentric cohort study in the medically assisted reproduction department of the University Hospital of Angers, France, between January 2017 and October 2020. Inclusion criteria were age >18 years old and one live birth after FET in an artificial cycle. The main outcome was the birth weight of the newborns. The choice of oestrogens administration (transdermal or vaginal) was left to the patient. RESULTS: 804 FET in artificial cycle were included in our study. Oestrogens were administrated in 356/804(36.6%) patients using transdermal route and in 448/804(45.9%) patients using vaginal route. There were 68/345 (19.1%) live births in the transdermal group and 85/448 (19%) in the vaginal group. There was no difference in the birth weight of the newborns (3320[2100-4165] grams in the transdermal group vs 3327.5[915-4650] grams in the vaginal group, p=0.72). All the other perinatal issues were comparable between the two groups. CONCLUSION: Birth weights and perinatal issues were comparable with regard to the route of administration of oestrogens (vaginal or transdermal) in the context of endometrial preparation before FET in an artificial cycle.
Administration, Cutaneous , Administration, Intravaginal , Birth Weight , Embryo Transfer/methods , Estradiol/administration & dosage , Adult , Cohort Studies , Cryopreservation , Estrogens/administration & dosage , Female , Humans , Live Birth , Pregnancy , Retrospective Studies
The importance of sexual dimorphism of the mouse brain metabolome was recently highlighted, in addition to a high regional specificity found between the frontal cortex, the cerebellum, and the brain stem. To address the origin of this dimorphism, we performed gonadectomy on both sexes, followed by a metabolomic study targeting 188 metabolites in the three brain regions. While sham controls, which underwent the same surgical procedure without gonadectomy, reproduced the regional sexual dimorphism of the metabolome previously identified, no sex difference was identifiable after gonadectomy, through both univariate and multivariate analyses. These experiments also made it possible to identify which sex was responsible for the dimorphism for 35 metabolites. The female sex contributed to the difference for more than 80% of them. Our results show that gonads are the main contributors to the brain sexual dimorphism previously observed, especially in females.
Metabolomics , Sex Characteristics , Animals , Brain , Castration , Female , Male , Metabolome , Mice
BACKGROUND: The best-known role of spermatozoa is to fertilize the oocyte and to transmit the paternal genome to offspring. These highly specialized cells have a unique structure consisting of all the elements absolutely necessary to each stage of fertilization and to embryonic development. Mature spermatozoa are made up of a head with the nucleus, a neck, and a flagellum that allows motility and that contains a midpiece with a mitochondrial helix. Mitochondria are central to cellular energy production but they also have various other functions. Although mitochondria are recognized as essential to spermatozoa, their exact pathophysiological role and their functioning are complex. Available literature relative to mitochondria in spermatozoa is dense and contradictory in some cases. Furthermore, mitochondria are only indirectly involved in cytoplasmic heredity as their DNA, the paternal mitochondrial DNA, is not transmitted to descendants. OBJECTIVE AND RATIONAL: This review aims to summarize available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility. SEARCH METHODS: PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews pertaining to human spermatozoa and mitochondria. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA', 'spermatozoa' or 'sperm' and 'reactive oxygen species' or 'calcium' or 'apoptosis' or signaling pathways'. These keywords were combined with other relevant search phrases. References from these articles were used to obtain additional articles. OUTCOMES: Mitochondria are central to the metabolism of spermatozoa and they are implicated in energy production, redox equilibrium and calcium regulation, as well as apoptotic pathways, all of which are necessary for flagellar motility, capacitation, acrosome reaction and gametic fusion. In numerous cases, alterations in one of the aforementioned functions could be linked to a decline in sperm quality and/or infertility. The link between the mitochondrial genome and the quality of spermatozoa appears to be more complex. Although the quantity of mtDNA, and the existence of large-scale deletions therein, are inversely correlated to sperm quality, the effects of mutations seem to be heterogeneous and particularly related to their pathogenicity. WIDER IMPLICATIONS: The importance of the role of mitochondria in reproduction, and particularly in gamete quality, has recently emerged following numerous publications. Better understanding of male infertility is of great interest in the current context where a significant decline in sperm quality has been observed.
Infertility, Male , Spermatozoa , DNA, Mitochondrial/genetics , Humans , Infertility, Male/genetics , Infertility, Male/metabolism , Male , Mitochondria/genetics , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/pharmacology , Sperm Motility , Spermatozoa/physiology
The mitochondria, present in almost all eukaryotic cells, produce energy but also contribute to many other essential cellular functions. One of the unique characteristics of the mitochondria is that they have their own genome, which is only maternally transmitted via highly specific mechanisms that occur during gametogenesis and embryogenesis. The mature oocyte has the highest mitochondrial DNA copy number of any cell. This high mitochondrial mass is directly correlated to the capacity of the oocyte to support the early stages of embryo development in many species. Indeed, the subtle energetic and metabolic modifications that are necessary for each of the key steps of early embryonic development rely heavily on the oocyte's mitochondrial load and activity. For example, epigenetic reprogramming depends on the metabolic cofactors produced by the mitochondrial metabolism, and the reactive oxygen species derived from the mitochondrial respiratory chain are essential for the regulation of cell signaling in the embryo. All these elements have also led scientists to consider the mitochondria as a potential biomarker of oocyte competence and embryo viability, as well as a key target for future potential therapies. However, more studies are needed to confirm these findings. This review article summarizes the past two decades of research that have led to the current understanding of mitochondrial functions in reproduction.
Cancer/Testis Antigens (CTAs) genes are expressed only during spermatogenesis and tumorigenesis. Both processes share common specific metabolic adaptation related to energy supply, with a glucose to lactate gradient, leading to changes in mitochondrial physiology paralleling CTAs expression. In this review, we address the role of CTAs in mitochondria (mitoCTAs), by reviewing all published data, and assessing the putative localization of CTAs by screening for the presence of a mitochondrial targeting sequence (MTS). We evidenced that among the 276 CTAs, five were already shown to interfere with mitochondrial activities and 67 display a potential MTS.
Antigens, Neoplasm/genetics , Mitochondria/metabolism , Neoplasms/genetics , Spermatogenesis , Antigens, Neoplasm/metabolism , Gene Expression Regulation, Neoplastic , Humans , Male , Mitochondria/genetics , Neoplasms/metabolism , Testis/metabolism
The aim of this study was to evaluate an oocyte pick-up (OPU) simulation training program for residents using the high fidelity PickUpSimTM (Accurate, Cesena, Italy) simulator. The authors carried out an observational study during an OPU simulation workshop. A successful scenario was defined as an oocyte retrieval rate ≥70% without any complications. Forty-six residents affiliated to 23 different French university hospitals were included, and 37/46 (80.4%) of them successfully completed the scenario with a mean time of 3.4 ± 1.1 minutes. The oocyte retrieval rate was 442/561 (78.8%). All residents found training beneficial and 41/46 (87%) were in favour of having simulation-based training programs for OPU in their reproductive medicine departments. All residents who had previous experience with OPU (11/11) recommended the use of a simulator before performing OPU. This study confirms that high-fidelity OPU simulation is a simple and efficient method for training residents.Impact statementWhat is already known on this subject? Simulator-based training has been shown to be effective and useful for oocyte pick-up (OPU) training.What the results of this study add? All residents found the simulation program beneficial and formative, with 80% successfully completing their scenarios in a mean time of 3.4 ± 1.1 minutes. All residents who had previous experience with OPU recommended the use of a simulator before performing OPU.What the implications are of these findings for clinical practice and/or further research? Prospective studies are needed to confirm the short- and long-term positive clinical impact of OPU simulation training programs.
Gynecology/education , Internship and Residency/methods , Obstetrics/education , Oocyte Retrieval/methods , Simulation Training/methods , Feasibility Studies , Female , Humans , Pregnancy , Surveys and Questionnaires
BACKGROUND: Male factor is incriminated in approximately 50% of cases of infertility. The metabolomic approach has recently been used in the assessment of sperm quality and male fertility. MATERIALS AND METHODS: We analyzed the metabolomic signatures of the seminal plasma in 20 men with severe oligoasthenospermia (prewash total motile sperm count < 5.106 ) (SOA) and compared it to 20 men with normal semen parameters, with a standardized approach of targeted and quantitative metabolomics using high-performance liquid chromatography, coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. RESULTS: Among the 188 metabolites analyzed, 110 were accurately measured in the seminal plasma. A robust model discriminating the two populations (Q2(cum) = 55.2%) was obtained by OPLS-DA (orthogonal partial least-squares discriminant analysis), based on the drop in concentrations of 37 metabolites with a VIP (variable important for projection) greater than 1. Overall, in men with SOA, there was a significant decrease in: 17 phosphatidylcholines and four sphingomyelins; acylcarnitines, with free L-carnitine being the most discriminating metabolite; polyunsaturated fatty acids; six amino acids (glutamate, aspartate, methionine, tryptophan, proline, and alanine); and four biogenic amines (spermine, spermidine, serotonin, and alpha-aminoadipate). DISCUSSION: Our signature includes several metabolic changes with different impacts on the sperm quality: a change in phospholipid composition and the saturation of their fatty acids that is potentially linked to the deterioration of sperm membranes; a carnitine deficiency that can negatively impact the energy production via fatty acid oxidation and oxidative phosphorylation; and a decreased level of amino acids and biogenic amines that can lead to dysregulated metabolic and signaling pathways. CONCLUSION: We provide a global overview of the metabolic defects contributing to the structural and functional alteration of spermatozoa in severe oligoasthenospermia. These findings offer new insights into the pathophysiology of male factor infertility that could help to develop future specific treatments.
Metabolome/physiology , Oligospermia/metabolism , Semen Analysis , Sperm Motility/physiology , Spermatozoa/pathology , Adult , Amines/analysis , Amino Acids/analysis , Carnitine/analogs & derivatives , Carnitine/analysis , Fatty Acids, Unsaturated/analysis , Humans , Male , Metabolomics/methods , Phosphatidylcholines/analysis , Prospective Studies , Semen/cytology , Sphingomyelins/analysis
Endometriosis and infertility are closely linked, but the underlying mechanisms are still poorly understood. This study aimed to evaluate the impact of endometriosis on in vitro fertilization (IVF) parameters, especially on embryo quality and IVF outcomes. A total of 1124 cycles with intracytoplasmic sperm injection were retrospectively evaluated, including 155 cycles with endometriosis and 969 cycles without endometriosis. Women with endometriosis had significantly lower ovarian reserve markers (AMH and AFC), regardless of previous ovarian surgery. Despite receiving significantly higher doses of exogenous gonadotropins, they had significantly fewer oocytes, mature oocytes, embryos, and top-quality embryos than women in the control group. Multivariate analysis did not reveal any association between endometriosis and the proportion of top-quality embryo (OR = 0.87; 95% CI [0.66-1.12]; p = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups (p = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, p = 0.001), as a consequence of the lower number of frozen embryos. In conclusion, endometriosis lowers the cumulative live birth rates by decreasing the number of embryos available to transfer, but not their quality.
PURPOSE: To determine the risk of multiple pregnancies (MP) following conversion of in vitro fertilization (IVF) cycles to intrauterine insemination (IUI) when a poor ovarian response (POR) is diagnosed during controlled ovarian stimulation (COS). METHODS: We undertook a retrospective study in our teaching hospital from January 2012 to December 2017. We included all IVF cycles with POR that were converted to IUI (<5 follicles ≥ 14 mm and peak estradiol level < 1000 pg/mL on trigger day). RESULTS: Overall, 205 IVF cycles that were converted to IUI in 128 patients were analyzed. Mean age was 34.1 ± 4.6 years, mean antral follicle count was 11 ± 5.3 and mean AMH was 1.8 ± 2.9 ng/L. The main causes of infertility were unexplained (41 %) (84/205) and diminished ovarian reserve (35 %) (72/205). Of all the cycles converted to IUI, 53 (26 %) had one mature follicle on trigger day, 56 (27 %) had 2, 56 (27 %) had 3, and 40 (20 %) had 4. The live birth rate (LBR) was 7.3 % (15/205), and the miscarriage rate was 28.6 % (6/21). There were 3 twin pregnancies, but no higher order pregnancies; the MP rate was 14.3 % (3/21). There was no significant difference in the MP rate between patients with 1-2 mature follicles and patients with 3-4 mature follicles (18.2 % vs 10 %, p = 0.99, respectively). CONCLUSION: In IVF cycles converted to IUI for poor response, the risk of MP is acceptable (14 %) with no higher order pregnancies, even with 3 or 4 follicles ≥14 mm on trigger day.
Fertilization in Vitro/methods , Insemination, Artificial/methods , Ovulation Induction/statistics & numerical data , Pregnancy, Multiple/statistics & numerical data , Abortion, Spontaneous/epidemiology , Adult , Female , Humans , Infertility/therapy , Ovarian Follicle/physiopathology , Ovarian Reserve/physiology , Pregnancy , Pregnancy Outcome , Pregnancy Rate , Pregnancy, Twin/statistics & numerical data , Retrospective Studies
To determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group (n = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high (n = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level (p = 0.002) and a significantly lower number of oocytes recovered (p = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis.
OBJECTIVE: Ovarian ageing is one of the commonest causes of infertility in patients consulting for assisted reproductive technology. The composition of the follicular fluid (FF), which reflects the exchanges between the oocyte and its microenvironment, has been extensively investigated to determine the metabolic pathways involved in various ovarian disorders. Considering the importance of cytokines in folliculogenesis, we focused on the cytokine profile of the FF during ovarian ageing. MATERIAL AND METHODS: Our cross-sectional study assesses the levels of 27 cytokines and growth factors in the FF of two groups of women undergoing in vitro fertilization. One group included 28 patients with ovarian ageing clinically characterized by a diminished ovarian reserve (DOR), and the other group included 29 patients with a normal ovarian reserve (NOR), serving as controls. RESULTS: With univariate analysis, the cytokine profile was found to differ significantly between the two groups. After adjustment of the p-values, platelet-derived growth factor-BB (PDGF-BB) was the only cytokine with a significantly lower concentration in the DOR group (7.34 ± 16.11 pg/mL) than in the NOR group (24.39 ± 41.38 pg/mL) (p = 0.005), independently of chronological age. CONCLUSION: Thus, PDGF-BB would seem to be implicated in the physiopathology of DOR, potentially in relation to its role in folliculogenesis or in the protection against oxidative stress.
Aging/physiology , Cytokines/analysis , Follicular Fluid/chemistry , Ovary/physiology , Adult , Cross-Sectional Studies , Female , Fertilization in Vitro , Humans , Infertility, Female/physiopathology , Infertility, Female/therapy , Ovarian Follicle/physiopathology , Ovarian Reserve/physiology , Proto-Oncogene Proteins c-sis
The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.
Embryo Transfer/methods , Endometrium/drug effects , Estrogens/administration & dosage , Patient Satisfaction , Pregnancy Outcome , Administration, Cutaneous , Administration, Intravaginal , Adult , Female , Humans , Pregnancy , Pregnancy Rate
