RESUMO
RESEARCH QUESTION: Is there a difference in perinatal outcome in the same patient cohort for babies conceived following randomization of sibling oocytes allocated to a simplified IVF culture system (SCS) or intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: The study compared the perinatal outcomes of 367 babies born from 1 January 2013 until 31 December 2020 after using split SCS and ICSI insemination of sibling oocytes in a selected group of normo-responsive women, excluding cases of severe male infertility. Primary outcome measures were preterm birth (PTB; <37 weeks' gestation), low birthweight (LBW; <2.5 kg) and small for gestational age (SGA) as a primary outcome parameter while secondary outcome measures included mean birthweight, mean gestational age, extreme prematurity (<32 weeks), very low birthweight (<1.5 kg), perinatal mortality, multiple pregnancy and Caesarean section rate. RESULTS: A total of 105 and 103 singleton babies were born after fresh embryo transfer (FRET) and 71 and 50 singletons after frozen embryo transfer (FET) in the SCS and ICSI groups, respectively. For babies born after FRET, the LBW rate was 2.9% (3/105) for SCS and 7.8% (8/103) for ICSI (Pâ¯=â¯0.10). LBW occurred in 4.2% (3/71) and 0% (0/50) of babies born after the transfer of cryopreserved-thawed SCS and ICSI embryos, respectively (Pâ¯=â¯0.14). The rate of PTB was 3.8% and 6.8% for SCS and ICSI in FRET cycles (Pâ¯=â¯0.33), and 8.5% and 6.0% for SCS and ICSI in FET cycles (Pâ¯=â¯0.62). One congenital malformation was found in the SCS FET group. CONCLUSION: There was no difference in perinatal outcome for singleton and twin babies born after SCS and ICSI.
Assuntos
Nascimento Prematuro , Injeções de Esperma Intracitoplásmicas , Peso ao Nascer , Cesárea , Estudos de Coortes , Feminino , Fertilização in vitro , Humanos , Recém-Nascido , Masculino , Oócitos , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Estudos Retrospectivos , SêmenRESUMO
The practice of ovarian stimulation for IVF is undergoing a fundamental re-evaluation as recent data begin to successfully challenge the traditional paradigm that ovarian stimulation should be aimed at the retrieval of as many oocytes as possible, in the belief that this will increase pregnancy rates. An opposing view is that live birth rate should not be the only end-point in evaluating the success of IVF treatment and that equal emphasis should be placed on safety and affordability. The International Society for Mild Approaches in Assisted Reproduction (ISMAAR) committee has carried out an up-to-date literature search, with the evidence being graded according to the University of Oxford's Centre for Evidence-Based Medicine. The recommendations were formulated taking into account the quality of evidence on the efficacy, risk and cost of each intervention. ISMAAR recommends adopting a mild approach to ovarian stimulation in all clinical settings as an increasing body of evidence suggests that mild stimulation is as effective as conventional stimulation, while being safer and less expensive. Mild ovarian stimulation could replace conventional stimulation, thus making IVF safer and more accessible worldwide.
Assuntos
Fertilização in vitro , Indução da Ovulação , Gravidez , Feminino , Humanos , Taxa de Gravidez , Coeficiente de Natalidade , ReproduçãoRESUMO
RESEARCH QUESTION: Can a novel closed simplified IVF culture system be used to achieve outcomes comparable to those obtained with intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: This analysis is part of a non-inferiority prospective study comparing ICSI and a simplified culture system (SCS) for gamete fertilization in a selected group of patients. According to protocol, sibling oocytes in intact cumulus-oocyte complexes were randomly distributed between ICSI and conventional insemination in the SCS. For women, selection criteria included being under 43 years of age and at least six eggs at retrieval. An inseminating motile sperm count ≥1 million was required. The primary outcome measure was ongoing pregnancy rate (>12 weeks) per cycle; secondary outcome measures included fertilization rate, miscarriage rate and implantation rate (ongoing pregnancy rate per embryo). RESULTS: From January 2016 until December 2019, 653 SCS/ICSI cycles were performed yielding a total of 7915 oocytes. The fertilization rate was 61.1% and 50.4% for SCS and ICSI (P < 0.0001), respectively. The ongoing pregnancy rate was 32.0% for SCS and 36.7% for ICSI (Pâ¯=â¯0.27). Implantation rate was 30.6% for SCS and 34.4% for ICSI (Pâ¯=â¯0.35). The miscarriage rate was 7.5% and 6.5% for SCS and ICSI, respectively (Pâ¯=â¯0.75). CONCLUSION: No difference was found in ongoing pregnancy rate, implantation rate and the miscarriage rate between SCS and ICSI in this selected patient cohort.
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Aborto Espontâneo , Fertilização in vitro , Aborto Espontâneo/epidemiologia , Transferência Embrionária , Feminino , Humanos , Masculino , Oócitos , Gravidez , Taxa de Gravidez , Estudos Prospectivos , SêmenRESUMO
Increased paternal age has been associated with lower fertility and higher genetic risk for the offspring. One way to prevent these consequences is to freeze sperm at a young age. Social sperm freezing could be developed in a way similar to social oocyte freezing. The main difference between freezing oocytes and sperm is that social sperm freezing is much less focussed on fertility preservation and much more on avoiding increased genetic risk. Contrary to what some people seem to believe, sperm freezing is more complicated than it looks at first sight. This article considers three practical aspects: freezing, storage and testing. It is concluded that the remedy (cryopreservation) may itself cause damage to the quality of the spermatozoon and to its genetic integrity, thus undoing the possible benefits in terms of fertility and health of offspring.
Assuntos
Preservação do Sêmen , Espermatozoides , Criopreservação , Fertilidade , Congelamento , Humanos , Masculino , Oócitos , Motilidade dos EspermatozoidesRESUMO
OBJECTIVE: To evaluate the long-term reproductive outcomes in patients with dysmorphic uterus treated by hysteroscopic metroplasty with miniaturized instruments. DESIGN: Retrospective multicenter cohort study. SETTING: Tertiary care university hospitals. PATIENTS: The study was conducted on 214 women with a dysmorphic uterus (T-shaped, infantilis, or other type of dysmorphic uterus according to the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy classification system) with history of primary unexplained infertility (group 1) or repeated (>2) early miscarriages (group 2). Dysmorphic uteri were diagnosed by office hysteroscopy and 3-dimensional transvaginal ultrasound (3D-TVS). INTERVENTIONS: All patients underwent in office hysteroscopic metroplasty using a continuous-flow hysteroscope with a 5 Fr operating channel introduced into the uterine cavity using the vaginoscopic approach. Longitudinal incisions were performed on the fibromuscular constriction rings in the isthmic area and in some cases on the other uterine walls with a 5 Fr bipolar electrode or scissors. At the end of the procedure, an antiadhesive gel was applied into the uterine cavity to minimize adhesion formation. Postsurgical assessment of the uterine cavity was carried out through office hysteroscopy and 3D-TVS. All patients were followed for at least 24 months. MEASUREMENTS AND MAIN RESULTS: The metroplasty was completed in all cases, resulting in a significant increase of uterine cavity volume (100%) and optimization of uterine morphology in 211 of 214 women (98.6%). After 60 months, the overall clinical pregnancy rate was 72.9% (nâ¯=â¯156/214), and the live birth rate was 80.1% (nâ¯=â¯125/156). Specifically, 74 of 156 women (47.4%) conceived spontaneously (with a median time to pregnancy of 5.5 months), of whom 32.4% had previously failed 1 or more attempts at in vitro fertilization/intracytoplasmic sperm injection. CONCLUSION: Our long-term follow-up data demonstrate that the hysteroscopic correction of dysmorphic uteri may result in a high live birth rate in women suffering from unexplained infertility or repeated miscarriages.
Assuntos
Histeroscopia , Infertilidade Feminina/etiologia , Infertilidade Feminina/cirurgia , Resultado da Gravidez/epidemiologia , Doenças Uterinas/cirurgia , Útero/anormalidades , Adulto , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Histeroscopia/efeitos adversos , Histeroscopia/métodos , Histeroscopia/estatística & dados numéricos , Infertilidade Feminina/epidemiologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Aderências Teciduais/epidemiologia , Aderências Teciduais/etiologia , Resultado do Tratamento , Anormalidades Urogenitais/cirurgia , Doenças Uterinas/congênito , Doenças Uterinas/patologia , Útero/patologia , Útero/cirurgiaRESUMO
PURPOSE: To prospectively evaluate and compare the junctional zone (JZ) and outer myometrial thickness in infertile and healthy nulliparous women at different locations in the uterine wall during the menstrual cycle by magnetic resonance imaging (MRI). MATERIALS AND METHODS: We performed pelvic 1.5T MRI (T2 -weighted turbo spin echo sequences) on 28 infertile women: 5 with infertility of unknown origin, 12 anovulating, and 11 on ovarian stimulation therapy (mean age 28.5, 30.8, and 29.3 years, respectively); and a control group consisting of 18 healthy nulliparous volunteers (mean age 26.4 years). The women with unknown infertility origin and the control group underwent MRI investigations during their follicular, ovulatory, and luteal phase. The JZ and outer myometrial thicknesses were measured at six locations in the uterine wall: anterior and posterior wall of the isthmus, midcorpus, and fundus. RESULTS: The JZ in the anovulating women at the posterior wall of the isthmus (4.2 mm) was significantly thicker compared to the control group (3.2, 3.0, and 2.9 mm, in respectively the three menstrual phases) (P = 0.027). The outer myometrium in the anovulating women was significantly thicker at all measured locations (average 11.5 mm) in comparison to the control group (8.1, 8.0, and 8.5 mm, in respectively the three menstrual phases) (P < 0.050). The infertile women on ovarian stimulation therapy showed a significantly thicker outer myometrium at the anterior wall (isthmus, midcorpus, and fundus) (P < 0.050). CONCLUSION: The results indicate that a thickened JZ, and especially a thickened outer myometrium, might be associated with infertility. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:926-936.
Assuntos
Infertilidade Feminina/diagnóstico por imagem , Infertilidade Feminina/patologia , Imageamento por Ressonância Magnética/métodos , Ciclo Menstrual , Miométrio/diagnóstico por imagem , Miométrio/patologia , Adulto , Biomarcadores , Feminino , Humanos , Tamanho do Órgão , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
This prospective study aims to determine the optimal menstrual phase and uterine location to detect the thickest junctional zone by magnetic resonance imaging (MRI). Healthy nulliparous women were subdivided according to their use of hormonal contraception. Each women was investigated three times during their menstrual cycle. Eighteen nulliparous non-users and 29 nulliparous users of hormonal contraception (mean age 26.4 and 25.8 years, respectively) underwent a pelvic MRI (1.5T) examination during the follicular, ovulatory and luteal phase. The junctional zone thickness was measured at six locations in the uterine wall. A significantly thinner junctional zone was observed at the anterior and posterior wall of the midcorpus (P = 0.01 and P = 0.004 respectively) and fundus (P = 0.009 and P = 0.023 respectively), in the contraception users compared with the non-users. No differences in junctional zone thickness were noticed between the menstrual phases and the uterine wall locations. The ratio of junctional zone versus total myometrial thickness was also different between both groups and between the assessed uterine locations. To conclude, any phase in the menstrual cycle and location within the uterine wall was validated to determine the junctional zone thickness on MRI, although the fundal location is preferred.
Assuntos
Anticoncepcionais Orais Hormonais/uso terapêutico , Ciclo Menstrual , Útero/fisiologia , Adulto , Anticoncepção , Feminino , Hormônios/uso terapêutico , Humanos , Fase Luteal , Imageamento por Ressonância Magnética , Estudos Prospectivos , Adulto JovemRESUMO
The aim was to examine the value of different covariates in the prediction of intrauterine insemination (IUI) success. Between July 2011 and September 2015, data from 1401 IUI cycles with homologous semen in 556 couples were collected prospectively, by questionnaire, in a tertiary referral infertility centre. Statistical analysis was performed using generalized estimating equations (GEEs). GEEs were used instead of an ordinary logistic regression model to take into account the correlation between observations from the same person. The primary outcome parameter was clinical pregnancy rate (CPR), confirmed with a gestational sac and fetal heartbeat on ultrasonography at 7-8 weeks. An overall CPR of 9.5% per cycle was observed. Univariate statistical analysis revealed female and male age, male smoking, female body mass index, ovarian stimulation and inseminating motile count (IMC) as covariates significantly influencing CPR per cycle. Multivariate GEE analysis revealed that the only valuable prognostic covariates included female age, male smoking and infertility status (i.e. primary/secondary infertility). IMC showed a significant curvilinear relationship, with first an increase and then a decrease in pregnancy rate.
Assuntos
Inseminação Artificial , Taxa de Gravidez , Sêmen , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
The extent to which certain parameters can influence pregnancy rates after intrauterine insemination with frozen donor semen was examined prospectively. Between July 2011 and September 2015, 402 women received 1264 IUI cycles with frozen donor semen in a tertiary referral infertility centre. A case report form was used to collect data prospectively. The primary outcome measure was clinical pregnancy rate (CPR), confirmed by detection of a gestational sac and fetal heartbeat using ultrasonography at 7-8 weeks of gestation. Statistical analysis was carried out using generalized estimating equations (GEE) to account for the correlation between observations from the same patient. Overall, CPR per cycle was 17.2%. Multivariate GEE analysis revealed the following parameters as predictive for a successful pregnancy outcome: female age (P = 0.0003), non-smoking or smoking fewer than 15 cigarettes a day (P = 0.0470 and P = 0.0235, respectively), secondary infertility (P = 0.0062), low progesterone levels at day zero of the cycle (P = 0.0164) and use of ovarian stimulation with HMG and recombinant FSH compared with clomiphene citrate and natural cycle (P = 0.0006 and P = 0.0004, respectively). These parameters were the most important factors influencing the success rate in a sperm donation programme.
Assuntos
Inseminação Artificial Heteróloga/estatística & dados numéricos , Taxa de Gravidez , Adulto , Criopreservação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Sêmen , Análise do Sêmen/estatística & dados numéricos , Espermatozoides , Adulto JovemRESUMO
Until very recently, the problem of infertility in developing countries has been ignored at all levels of healthcare management. Because many preventable or treatable diseases still claim millions of lives, and due to limited resources, provision of infertility care is not on the resource allocation agenda at all, prevention of sexually transmitted diseases remaining the number one priority. Tubal infertility due to sexually transmitted diseases, unsafe abortion and post-partum pelvic infections is the main cause of infertility. Most cases are only treatable with assisted reproduction technology, which are either unavailable or too costly. In December 2007, an expert meeting was organized in Arusha, Tanzania by the Walking Egg non-profit organization in co-operation with ESHRE. The meeting was the start of a global project aimed at increasing diagnostic and therapeutic options for childless couples in resource-poor countries. From the start, the Walking Egg Project has approached this problem in a multidisciplinary and global manner. It gathers medical, social, ethical, epidemiological, juridical and economic scientists to discuss and work together towards its goal. The final objective of the Walking Egg Project is the implementation of infertility services in many developing countries, preferably integrated in existing family planning and mother care services.
Assuntos
Acessibilidade aos Serviços de Saúde , Infertilidade/terapia , Técnicas de Reprodução Assistida , Adulto , Países em Desenvolvimento , Feminino , Humanos , Masculino , Organizações sem Fins Lucrativos , Fatores SocioeconômicosRESUMO
Many variables may influence success rates after intrauterine insemination (IUI), including sperm quality in the native and washed semen sample. A literature search was performed to investigate the threshold levels of sperm parameters above which IUI pregnancy outcome is significantly improved and/or the cut-off values reaching substantial discriminative performance in an IUI programme. A search of MEDLINE, EMBASE and Cochrane Library revealed a total of 983 papers. Only 55 studies (5.6%) fulfilled the inclusion criteria and these papers were analysed. Sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value ⩾5% normal morphology; (iii) total motile sperm count in the native sperm sample: cut-off value of 5-10 million; and (iv) total motility in the native sperm sample: threshold value of 30%. The results indicate a lack of prospective studies, a lack of standardization in semen testing methodology and a huge heterogeneity of patient groups and IUI treatment strategies. More prospective cohort trials and prospective randomized trials investigating the predictive value of semen parameters on IUI outcome are urgently needed. It is generally believed that intrauterine insemination (IUI) with homologous semen should be a first-choice treatment to more invasive and expensive techniques of assisted reproduction in cases of cervical, unexplained and moderate male factor subfertility. The rationale for the use of artificial insemination is to increase gamete density at the site of fertilization. Scientific validation of this strategy is difficult because literature is rather confusing and inconclusive. Many variables may influence success rates after IUI treatment procedures. It seems logical that sperm quality has to be one of the main determinants to predict IUI success. Clinical practice would benefit from the establishment of threshold levels for sperm parameters above which IUI pregnancy outcome is significantly improved and below which a successful outcome is unlikely. We performed a literature search to investigate if such threshold levels are known. Most striking were the lack of standardization in semen-testing methodology and the huge heterogeneity of patient groups and IUI treatment strategies. The four sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value >4% normal morphology; (iii) total motile sperm count in native sperm sample: cut-off value of 5-10 million; and (iv) total motility in native sperm sample: threshold value of 30%. This review identified an urgent need for more and better prospective cohort trials investigating the predictive value of semen parameters on IUI pregnancy rate.
Assuntos
Resultado da Gravidez , Análise do Sêmen , Feminino , Humanos , Inseminação Artificial , Masculino , Gravidez , Estudos RetrospectivosRESUMO
This study investigated the effects of long-term (24h) in-vitro sperm incubation at room temperature (RT; 23°C) versus testis temperature (35°C) on various sperm-quality parameters. Semen samples (n=41) were prepared both by density-gradient centrifugation (DGC) and the swim-up technique in order to compare the influence of sperm preparation on sperm quality after incubation. Progressive motility and morphology were significantly higher after incubation at RT compared with 35°C (P<0.001 and P<0.01, respectively). The proportions of acrosome-reacted, apoptotic and dead spermatozoa were significantly lower in samples incubated for 24h at RT compared with 35°C (P<0.001, P=0.01 and P<0.001, respectively). The number of motile, morphologically normal, non-acrosome-reacted and nonapoptotic spermatozoa recovered after sperm preparation was significantly higher in DGC compared with swim-up samples (P<0.001). However, spermatozoa prepared by swim-up showed better survival after incubation compared with DGC-prepared spermatozoa, especially when incubated at 35°C. In conclusion, this study indicates a significantly better and longer preservation of sperm quality when incubation is performed at RT. These findings may convince laboratories to change the routinely used sperm storage conditions in order to maximize the quality of the prepared sperm sample.
Assuntos
Separação Celular/métodos , Preservação do Sêmen/métodos , Centrifugação com Gradiente de Concentração , Humanos , Masculino , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides , TemperaturaRESUMO
This study reports the outcome results from a pilot clinical trial using a simplified laboratory method for human IVF. This system reproducibly generates de novo the atmospheric and culture conditions that support normal fertilization and preimplantation embryogenesis to the hatched blastocyst stage without the need for specialized medical-grade gases or equipment. Development from insemination to the hatched blastocyst stage occurs undisturbed in a completely closed system that enables timed performance assessments for embryo selection in situ that, in this study, involved single-embryo transfers on day 3. With the simplified culture system, 8/23 embryos implanted, one miscarried at 8weeks of gestation and seven healthy babies have been born. The methodology and results are discussed with regard to how this simplified system can be adopted worldwide to meet the growing need for accessible and affordable IVF. A common notion concerning the demographics of infertility is that it is largely a phenomenon associated with developed countries, where infertility treatments are commonplace. In fact, most infertile couples reside in developing/low-resource countries where infertility diagnosis and treatment is nonexistent, inaccessible or unaffordable by the vast majority of young men and women in need. The irony of this situation is that bilateral tubal occlusions, for which IVF was originally indicated and is the most effective treatment, is by far the most common cause of their infertility. We have addressed one aspect of this issue, the IVF laboratory, as part of a wider effort by the Walking Egg Project to design and establish small, dedicated centres in developing countries to provide assisted reproduction technologies that are affordable and accessible to a wider proportion of the population in need. The methods for conventional IVF designed to addresses tubal obstructions are relatively simple and free of complex instrumentation and the highly developed infrastructure common to high-resource centres. This simplified IVF system self-generates culture conditions in a closed system. After prolonged preclinical testing, a pilot clinical study was initiated in 2012 in Genk, Belgium. The findings suggest that a significant first step has been achieved in the effort to bring advanced assisted reproduction to developed countries using a low-resource but highly effective IVF system capable of bringing modern reproductive medicine to infertile couples in low-resource societies.
Assuntos
Fertilização in vitro/métodos , Animais , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário , Feminino , Humanos , Cinética , Camundongos , Projetos Piloto , Gravidez , Resultado da GravidezRESUMO
Infertility affects millions worldwide, with significant medical, financial, and emotional challenges, particularly in low- and middle-income countries (LMICs). Cultural, religious, financial, and gender-related barriers hinder access to treatment, exacerbating social and economic consequences, especially for women. Despite its prevalence, infertility often remains overlooked due to competing health priorities. However, global initiatives recognise infertility as a reproductive health concern, advocating for universal access to high-quality fertility care. In LMICs, limited resources and infrastructure impede access to treatment, prompting people to turn to alternative, often ineffective, non-biomedical solutions. Addressing these challenges requires implementing affordable fertility care services tailored to local contexts, supported by political commitment and community engagement. Emerging technologies offer promising solutions, but comprehensive education and training programs are essential for their effective implementation. By integrating fertility care into broader health policies and fostering partnerships, we can ensure equitable access to infertility treatment and support reproductive health worldwide.
Assuntos
Países em Desenvolvimento , Infertilidade , Serviços de Saúde Reprodutiva , Infertilidade/terapia , Preservação da Fertilidade , Serviços de Saúde Reprodutiva/economia , Serviços de Saúde Reprodutiva/normas , Acessibilidade aos Serviços de Saúde , Fatores Socioeconômicos , Religião , Custos e Análise de Custo , HumanosRESUMO
BACKGROUND: We developed a simplified IVF culture system (SCS) which has proven to be effective and safe in a selected IVF cohort. METHODS: Preterm birth (PTB) and low birth weight (LBW) of 175 singletons born after using the SCS, 104 after fresh embryo transfer (ET), and 71 after frozen embryo transfer, were compared with all singletons born in Flanders between 2012 and 2020 conceived after natural conception, ovarian stimulation (OS), and assisted reproduction (IVF/ICSI). FINDINGS: The proportion of preterm (<37 weeks) births was significantly higher in the case of IVF or ICSI, followed by hormonal treatment, compared to spontaneous pregnancies. There was no significant difference in PTB between SCS and any of the other groups. Concerning the average birth weight we found no significant difference between singletons born after natural conception and SCS. However, a significant difference in average birth weight was found between SCS singletons and singletons born after IVF, ICSI and hormonal treatment, with a significantly higher birth weight in the SCS group. This difference was also observed in the proportion of babies weighing less than 2500 g, with significantly more LBW babies in the IVF and ICSI group compared to the SCS newborns. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons were found to be comparable with singletons born after natural conception. Compared to babies born after ovarian stimulation and IVF/ICSI, SCS singletons had a lower PTB and LBW rates, although the differences were not significant for PTB. Our results confirm previous reports on reassuring perinatal outcomes after using the SCS technology.
RESUMO
BACKGROUND: Short- and long-term implications of SARS-CoV-2 on the quality of the sperm and the results of this on fertility remain largely unknown due to lack of longitudinal studies. In this longitudinal observational cohort study, we aimed to analyse the differential effect and the impact of SARS-CoV-2 infection on different semen quality parameters. METHODS: Sperm quality was assessed using the World Health Organization criteria, DNA damage to sperm cells by quantifying the DNA fragmentation index (DFI) and the high-density stainability (HDS), IgA- and IgG-anti-sperm antibodies (ASA) were assessed with light microscopy. FINDINGS: SARS-CoV-2 infection was associated with sperm parameters that were independent of spermatogenic cycle like progressive motility, morphology, DFI and HDS, as well as spermatogenic cycle dependent parameters such as sperm concentration. Detection of IgA- and IgG-ASA allowed classification of patients in three different groups according to its sequence of appearance in sperm during post-COVID-19 follow-up. The maximum progressive motility was lowest during follow-up in patients without ASA (41.9%), intermediate in patients with only IgA-ASA (46.2%) and highest inpatients who had both IgA- and IgG-ASA (54.9%). INTERPRETATION: SARS-CoV-2 infection was associated with changes of all analysed sperm parameters to a different degree which is also observed in their return to normality and is suggestive of individual variations in the patient's immune system performance. Firstly, sperm production is decreased through temporal immune mediated arrest of active meiosis, and secondly immune induced sperm DNA damage prevents fertilization if transferred to the oocyte. Both mechanisms are temporal, and most sperm parameters return to baseline after infection. FUNDING: AML (R20-014), Femicare.
Assuntos
COVID-19 , Análise do Sêmen , Humanos , Seguimentos , Análise do Sêmen/métodos , Estudos Prospectivos , Cromatina , SARS-CoV-2 , Estudos Longitudinais , Imunoglobulina A , Imunoglobulina G , Fragmentação do DNA , SêmenRESUMO
BACKGROUND: Assisted reproductive techniques services are often not accessible to the majority of infertile couples in Low and Middle Income Countries (LMIC) due to high costs. Lowering IVF laboratory costs is a crucial step to make IVF affordable for a larger part of the world population. We developed a simplified culture system (SCS) which has proven to be effective, and the next step is to prove its safety. METHODS: Preterm birth (PTB) and low birthweight (LBW) of 176 singletons born after using the SCS, 105 after fresh embryo transfer (fresh ET), and 71 after frozen embryo transfer (frozen ET) were compared with all IVF/ICSI singletons born in Belgium between 2013 and 2018. When comparing our 105 SCS babies born after fresh ET with all Belgian babies born after conventional IVF only, we also adjusted for 7 risk factors known to influence perinatal outcome, namelythe mother's age, day of transfer, pituitary inhibition protocol, rank of cycles, number of oocytes retrieved, number of embryos transferred, and gender of the baby. FINDINGS: Before adjustment, we found a significantly higher PTB (10.2% vs. 3.8%, OR 2.852, 95% CI [1.042-7.803], p-value 0.0413) and LBW (9.8% vs. 2.9%, OR 3.692, 95% CI [1.163-11.721], p-value 0.0267) in the conventional IVF group versus SCS after fresh ET. After adjusting for seven risk parameters, these differences remained significant (PTB: OR 2.627, 95% CI [1.013-6.816], p-value 0.0471) and LBW: OR 3.267, 95% CI [1.118-9.549], p-value 0.0305). PTB and LBW between both groups was not significantly different for singletons born after frozen ET. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons in FRET cycles are very reassuring and significantly lower compared to babies born after conventional IVF in Belgium. Being aware of its effectiveness, our results offer a good perspective for SCS to become an important tool to implement low-cost IVF in LMIC.
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OBJECTIVE: To study the contagiousness of sperm and its influence on fertility after recovery from COVID-19 infection. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENT(S): One hundred twenty Belgian men who had recovered from proven COVID-19 infection. INTERVENTION(S): No intervention was performed. MAIN OUTCOME MEASURE(S): Semen quality was assessed using the World Health Organisation criteria. DNA damage to sperm cells was assessed by quantifying the DNA fragmentation index and the high density stainability. Finally antibodies against SARS-CoV2 spike-1 antigen, nuclear and S1-receptor binding domain were measured by Elisa and chemilumenscent microparticle immunoassays, respectively. RESULT(S): SARS-CoV-2 RNA was not detected in semen during the period shortly after infection nor at a later time. Mean progressive motility was reduced in 60% of men tested shortly (<1 month) after COVID-19 infection, 37% of men tested 1 to 2 months after COVID-19 infection, and 28% of men tested >2 months after COVID-19 infection. Mean sperm count was reduced in 37% of men tested shortly (<1 month) after COVID-19 infection, 29% of men tested 1 to 2 months after COVID-19 infection, and 6% of men tested >2 months after COVID-19 infection. The severity of COVID-19 infection and the presence of fever were not correlated with sperm characteristics, but there were strong correlations between sperm abnormalities and the titers of SARS-CoV-2 IgG antibody against spike 1 and the receptor- binding domain of spike 1, but not against nucleotide, in serum. High levels of antisperm antibodies developed in three men (2.5%). CONCLUSION(S): Semen is not infectious with SARS-CoV-2 at 1 week or more after COVID-19 infection (mean, 53 days). However, couples with a desire for pregnancy should be warned that sperm quality after COVID-19 infection can be suboptimal. The estimated recovery time is 3 months, but further follow-up studies are under way to confirm this and to determine if permanent damage occurred in a minority of men.
Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/virologia , RNA Viral/análise , SARS-CoV-2/genética , Sêmen/virologia , Espermatozoides/fisiologia , Adulto , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , COVID-19/transmissão , Dano ao DNA , Fragmentação do DNA , Humanos , Imunoglobulina G/sangue , Infertilidade Masculina/virologia , Masculino , Estudos Prospectivos , SARS-CoV-2/imunologia , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/anormalidades , Espermatozoides/química , Glicoproteína da Espícula de Coronavírus/imunologiaAssuntos
Maus-Tratos Infantis , Transtornos Relacionados ao Uso de Substâncias , Criança , Humanos , Lactente , NigériaRESUMO
We wanted to determine the sperm DNA fragmentation index (DFI) cutoff for clinical pregnancies in women receiving intra-uterine insemination (IUI) with this sperm and to assess the contribution of Human Papillomavirus (HPV) infection on sperm DNA damage and its impact on clinical pregnancies. Prospective non-interventional multi-center study with 161 infertile couples going through 209 cycles of IUI in hospital fertility centers in Flanders, Belgium. Measurement of DFI and HPV DNA with type specific quantitative PCRs (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) in sperm before its use in IUI. Clinical pregnancy (CP) rate was used as the outcome to analyze the impact on fertility outcome and to calculated the clinical cutoff value for DFI. A DFI criterion value of 26% was obtained by receiver operating characteristic (ROC) curve analysis. Couples with a male DFI > 26% had significantly less CPs than couples with DFI below 26% (OR 0.0326; 95% CI 0.0019 to 0.5400; p = 0.017). In sperm, HPV prevalence was 14.8%/IUI cycle. Sperm samples containing HPV had a significantly higher DFI compared to HPV negative sperm samples (29.8% vs. 20.9%; p = 0.011). When HPV-virions were present in sperm, no clinical pregnancies were observed. More than 1 in 5 of samples with normal semen parameters (17/78; 21.8%) had an elevated DFI or was HPV positive. Sperm DFI is a robust predictor of clinical pregnancies in women receiving IUI with this sperm. When DFI exceeds 26%, clinical pregnancies are less likely and in vitro fertilization techniques should be considered.