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2.
Elife ; 102021 10 12.
Article in English | MEDLINE | ID: covidwho-1478420

ABSTRACT

Polygenic risk scores (PRSs) have been offered since 2019 to screen in vitro fertilization embryos for genetic liability to adult diseases, despite a lack of comprehensive modeling of expected outcomes. Here we predict, based on the liability threshold model, the expected reduction in complex disease risk following polygenic embryo screening for a single disease. A strong determinant of the potential utility of such screening is the selection strategy, a factor that has not been previously studied. When only embryos with a very high PRS are excluded, the achieved risk reduction is minimal. In contrast, selecting the embryo with the lowest PRS can lead to substantial relative risk reductions, given a sufficient number of viable embryos. We systematically examine the impact of several factors on the utility of screening, including: variance explained by the PRS, number of embryos, disease prevalence, parental PRSs, and parental disease status. We consider both relative and absolute risk reductions, as well as population-averaged and per-couple risk reductions, and also examine the risk of pleiotropic effects. Finally, we confirm our theoretical predictions by simulating 'virtual' couples and offspring based on real genomes from schizophrenia and Crohn's disease case-control studies. We discuss the assumptions and limitations of our model, as well as the potential emerging ethical concerns.


Subject(s)
Crohn Disease/genetics , Fertilization in Vitro , Genetic Testing , Models, Genetic , Multifactorial Inheritance , Preimplantation Diagnosis , Schizophrenia/genetics , Computer Simulation , Female , Genetic Predisposition to Disease , Humans , Male , Predictive Value of Tests , Pregnancy , Risk Assessment , Risk Factors
4.
Hum Reprod ; 36(9): 2506-2513, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1345732

ABSTRACT

STUDY QUESTION: Does the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function? SUMMARY ANSWER: We were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function. WHAT IS KNOWN ALREADY: No research data are available yet. STUDY DESIGN, SIZE, DURATION: This is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic. PARTICIPANTS/MATERIALS, SETTING, METHODS: A consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers. MAIN RESULTS AND THE ROLE OF CHANCE: Both COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality. LIMITATIONS, REASONS FOR CAUTION: This is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle. STUDY FUNDING/COMPETING INTEREST(S): The study was funded out of an internal budget. There are no conflicts of interest for any of the authors. TRIAL REGISTRATION NUMBER: CinicalTrials.gov registry number NCT04822012.


Subject(s)
COVID-19 , Ovarian Follicle , SARS-CoV-2 , COVID-19 Vaccines , Cohort Studies , Female , Fertilization in Vitro , Humans , Ovarian Follicle/physiopathology , RNA, Messenger , Vaccination
5.
Cells ; 10(7)2021 07 02.
Article in English | MEDLINE | ID: covidwho-1323125

ABSTRACT

The open carrier system (OC) is used for vitrification due to its high efficiency in preserving female fertility, but concerns remain that it bears possible risks of cross-contamination. Closed carrier systems (CC) could be an alternative to the OC to increase safety. However, the viability and developmental competence of vitrified/warmed (VW) oocytes using the CC were significantly lower than with OC. We aimed to improve the efficiency of the CC. Metaphase II oocytes were collected from mice after superovulation and subjected to in vitro fertilization after vitrification/warming. Increasing the cooling/warming rate and exposure time to cryoprotectants as key parameters for the CC effectively improved the survival rate and developmental competence of VW oocytes. When all the conditions that improved the outcomes were applied to the conventional CC, hereafter named the modified vitrification/warming procedure using CC (mVW-CC), the viability and developmental competence of VW oocytes were significantly improved as compared to those of VW oocytes in the CC. Furthermore, mVW-CC increased the spindle normality of VW oocytes, as well as the cell number of blastocysts developed from VW oocytes. Collectively, our mVW-CC optimized for mouse oocytes can be utilized for humans without concerns regarding possible cross-contamination during vitrification in the future.


Subject(s)
Blastocyst/cytology , Cryopreservation/methods , Fertilization in Vitro/methods , Oocytes/cytology , Vitrification , Animals , Biomarkers/metabolism , Blastocyst/metabolism , CDX2 Transcription Factor/genetics , CDX2 Transcription Factor/metabolism , Cadherins/genetics , Cadherins/metabolism , Cell Survival/drug effects , Cells, Cultured , Cryoprotective Agents/pharmacology , Dimethyl Sulfoxide/pharmacology , Ethylene Glycol/pharmacology , Female , Gene Expression , Male , Metaphase , Mice , Oocytes/drug effects , Oocytes/metabolism , Spermatozoa/physiology , Sucrose/pharmacology
6.
Reprod Biomed Online ; 43(3): 491-493, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316615

ABSTRACT

RESEARCH QUESTION: Is a symptom questionnaire as per the French IVF guidelines adequate for screening patients during the COVID-19 pandemic? DESIGN: Patients planning IVF from June 2020 to February 2021 were included in the study. In compliance with French IVF guidelines, all patients fever-free on the day of oocyte retrieval were screened for risk of COVID-19 by completing a symptom questionnaire after being counselled regarding the importance of a COVID-19-free medical practice. Patients with IVF planned between June and September 2020 only completed the questionnaire (group 1), while those planning IVF after September 2020 also underwent the RT-PCR test for SARS-CoV-2 RNA (group 2). Cycle cancellation rates between groups were compared. Group 1 patients consented for follicular fluid testing for SARS-CoV-2 and an interview after cycle completion to determine COVID-19 exposure during the 6 months before and after retrieval. RESULTS: Cycle cancellation rates for groups 1 and 2 were 0% (0/214) versus 1.4% (8/577), respectively, (P = 0.116). All 183 follicular fluid samples from group 1 were negative for SARS-CoV-2 RNA. Of 171 patients interviewed post-IVF, 16 (93.4%) developed COVID-19 symptoms or a positive real-time PCR (RT-PCR) RT-PCR test, but none within 2 months pre- or post-retrieval. CONCLUSIONS: These results provide reassurance that, consistent with the COVID-19 French IVF guidelines, use of a symptom questionnaire is effective in screening patients planning to undergo IVF. Failure to detect viral RNA in any follicular fluid sample does not negate the possibility that follicular fluid is a viral reservoir. However, the findings provide reassurance that the follicular environment in this study's carefully screened population was COVID-free.


Subject(s)
COVID-19 , Pandemics , Female , Fertilization in Vitro , Humans , RNA, Viral , SARS-CoV-2
7.
J Endocrinol ; 249(1): 57-70, 2021 04.
Article in English | MEDLINE | ID: covidwho-1314460

ABSTRACT

Vaspin is a novel adipokine mainly expressed in visceral adipose tissue and closely related to obesity and insulin-resistance. Currently, data about its ovarian expression are limited to animal models and its role in human reproduction is largely unexplored. Our study's aims were then to characterise vaspin expression in the human ovary and to study in vitro its effects on granulosa cells physiology. Secondly, we assessed vaspin and its receptor GRP78 variations in granulosa cells and follicular fluid of a cohort of 112 infertile women undergoing an in vitro fertilisation procedure and allocated to three groups, each including normal-weight and obese subjects: 34 PCOS patients, 33 women with isolated polycystic ovary morphology (ECHO group) and 45 controls. Vaspin and GRP78 expression in the ovary was assessed by immunohistochemistry, RT-qPCR and Western blot. Granulosa cells and follicular fluid were analysed by RT-qPCR and ELISA, respectively. In vitro, granulosa cells metabolism was studied after stimulation with recombinant human vaspin, with and without a siRNA directed against GRP78. Vaspin was highly expressed in the human ovary and concentration-dependently enhanced granulosa cells steroidogenesis, proliferation and viability through GRP78 (P < 0.0001). Vaspin levels in both granulosa cells and follicular fluid were significantly higher in obese women (P < 0.0001) and in the normal-weight ECHO group (P < 0.001), which also had the highest expression rates of GRP78 (P < 0.05). Although further investigation is needed, vaspin appears as a novel modulator of human granulosa cells physiology and possibly plays a role in PCOS pathogenesis, notably protecting from insulin-resistance induced complications.


Subject(s)
Granulosa Cells/physiology , Heat-Shock Proteins/physiology , Polycystic Ovary Syndrome/physiopathology , Serpins/physiology , Adult , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Fertilization in Vitro , Follicular Fluid/chemistry , France , Gene Expression , Granulosa Cells/chemistry , Granulosa Cells/drug effects , Heat-Shock Proteins/analysis , Heat-Shock Proteins/genetics , Humans , Infertility, Female/therapy , Insulin Resistance/physiology , Obesity/metabolism , Ovary/chemistry , Ovary/metabolism , RNA, Messenger/analysis , Serpins/genetics , Serpins/pharmacology , Steroids/biosynthesis
9.
Sci Rep ; 11(1): 14149, 2021 07 08.
Article in English | MEDLINE | ID: covidwho-1303789

ABSTRACT

Cryopreservation of mouse spermatozoa is widely used for the efficient preservation and safe transport of valuable mouse strains. However, the current cryopreservation method requires special containers (plastic straws), undefined chemicals (e.g., skim milk), liquid nitrogen, and expertise when handling sperm suspensions. Here, we report an easy and quick (EQ) sperm freezing method. The main procedure consists of only one step: dissecting a single cauda epididymis in a microtube containing 20% raffinose solution, which is then stored in a -80 °C freezer. The frozen-thawed spermatozoa retain practical fertilization rates after 1 (51%) or even 3 months (25%) with the C57BL/6 J strain, the most sensitive strain for sperm freezing. More than half of the embryos thus obtained developed into offspring after embryo transfer. Importantly, spermatozoa stored at -80 °C can be transferred into liquid nitrogen for indefinite storage. As far as we know, our EQ method is the easiest and quickest method for mouse sperm freezing and should be applicable in all laboratories without expertise in sperm cryopreservation. This technique can help avoid the loss of irreplaceable strains because of closure of animal rooms in emergency situations such as unexpected microbiological contamination or social emergencies such as the COVID-19 threat.


Subject(s)
Cryopreservation/methods , Semen Preservation/methods , Animals , COVID-19 , Cryopreservation/instrumentation , Embryo Transfer , Emergencies , Female , Fertilization in Vitro/methods , Male , Mice, Inbred C57BL , Semen Preservation/instrumentation
10.
Syst Biol Reprod Med ; 67(4): 260-269, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1249263

ABSTRACT

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is an unprecedented global situation, and all countries have adopted their own measurements to mitigate the spread of the virus in the first as well as in the subsequent waves of infection. All measures, especially in the first wave of the pandemic, were in combination with recommendations provided by professional and scientific organizations. Similar measures were applied to specific procedures, such as the management of infertility, including in vitro fertilization-embryo transfer (IVF-ET) treatments. Although there is no clear scientific evidence yet that the SARS-CoV-2 may exert negative effects on IVF outcome, especially at the early stages, several clinical reports indicate that the virus may impact male fertility through specific receptors presented at the somatic cells of the testis and used by the virus in order to gain entry to the respective cells. Nevertheless, it is not unreasonable to suspect that the virus may affect sperm function as well as oocyte performance directly through specific receptors or indirectly through other signaling pathways. Despite the good practice of IVF laboratory techniques, culture media may also be contaminated during equilibration when airborne virus's particles can contaminate culture media from an already infected embryology area or staff. Furthermore, although there is no clinical evidence, liquid nitrogen could be a route of infection for gametes and embryos when it has been contaminated during production or transportation. Therefore, cryopreservation of gametes and embryos must be virus-free. This communication aims to provide some aspects of the possible impact of the virus on gametes and embryos and how it may affect the cryopreservation procedures.Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CDC: Centers for Disease Control and Prevention; COVID-19: coronavirus disease 2019; ESHRE: European Society of Human Reproduction and Embryology; ET: embryo transfer; FSH: follicle stimulating hormone; IFFS: International Federation of Fertility Societies; IVF: in vitro fertilization; LH: luteinizing hormone; LN: liquid nitrogen; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; T: testosterone; WHO: World Health Organization.


Subject(s)
Blastocyst/virology , COVID-19/virology , Cryopreservation , Infertility/therapy , Oocytes/virology , Reproductive Techniques, Assisted , SARS-CoV-2/pathogenicity , Spermatozoa/virology , COVID-19/diagnosis , COVID-19/transmission , Embryo Transfer , Female , Fertilization in Vitro , Humans , Infertility/diagnosis , Infertility/physiopathology , Male , Pregnancy , Reproductive Techniques, Assisted/adverse effects
12.
Reprod Biol Endocrinol ; 19(1): 69, 2021 May 13.
Article in English | MEDLINE | ID: covidwho-1228997

ABSTRACT

OBJECTIVE: No information exists in the literature regarding the effect of mRNA SARS-CoV-2 vaccine on subsequent IVF cycle attempt. We therefore aim to assess the influence of mRNA SARS-CoV-2 vaccine on IVF treatments. DESIGN: An observational study. SETTING: A tertiary, university-affiliated medical center. PATIENTS AND METHODS: All couples undergoing consecutive ovarian stimulation cycles for IVF before and after receiving mRNA SARS-CoV-2 vaccine, and reached the ovum pick-up (OPU) stage. The stimulation characteristics and embryological variables of couples undergoing IVF treatments after receiving mRNA SARS-CoV-2 vaccine were assessed and compared to their IVF cycles prior to vaccination. MAIN OUTCOME MEASURES: Stimulation characteristics and embryological variables. RESULTS: Thirty-six couples resumed IVF treatment 7-85 days after receiving mRNA SARS-CoV-2 vaccine. No in-between cycles differences were observed in ovarian stimulation and embryological variables before and after receiving mRNA SARS-CoV-2 vaccination. CONCLUSIONS: mRNA SARS-CoV-2 vaccine did not affect patients' performance or ovarian reserve in their immediate subsequent IVF cycle. Future larger studies with longer follow-up will be needed to validate our observations.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Embryo Transfer , Fertilization in Vitro , SARS-CoV-2/immunology , Adult , Female , Humans , Infertility/therapy , Male , Ovarian Reserve , Ovulation Induction , Pregnancy , RNA, Messenger , Treatment Outcome
13.
Gynecol Endocrinol ; 37(10): 895-897, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1223203

ABSTRACT

OBJECTIVE: No information exists in the literature regarding the effect of coronavirus disease 19 (COVID-19) infection on subsequent in vitro fertilization (IVF) cycle attempt. We, therefore, aim to assess the influence of COVID-19 infection on IVF treatments. DESIGN: An observational study. SETTING: A tertiary, university-affiliated medical center. PATIENTS AND METHODS: All consecutive couples undergoing ovarian stimulation (OS) for IVF, before and after recovering from COVID-19 infection, and reached the ovum pick-up (OPU) stage. The stimulation characteristics and embryological variables of couples undergoing IVF treatments after recovering from COVID-19 infection were assessed and compared to their IVF cycles prior to COVID-19 infection. MAIN OUTCOME MEASURES: Stimulation characteristics and embryological variables. RESULTS: Nine couples (seven with the female partner infection and two with the male partner) resumed IVF treatment 8-92 d after recovering from the COVID-19 infection (negative polymerase chain reaction [PCR]). No in-between cycles differences were observed in OS and embryological variables between the cycles before and after recovering from the COVID-19 infection, except for a significantly lower proportion of top-quality embryos. CONCLUSIONS: COVID-19 infection did not affect patients' performance or ovarian reserve in their immediate subsequent IVF cycle, except for a reduced proportion of top-quality embryos (TQEs). We therefore suggest, to postpone IVF treatment for a least 3 months (duration of folliculogenesis and spermatogenesis) after recovering from COVID-19 infection, aiming to recruit healthy gametes that were not exposed to COVID-19 infection during their development.


Subject(s)
COVID-19/physiopathology , Embryo Transfer/statistics & numerical data , Fertilization in Vitro/statistics & numerical data , SARS-CoV-2 , Treatment Outcome , Adult , COVID-19/epidemiology , Embryo, Mammalian/physiopathology , Female , Humans , Male , Ovarian Reserve , Ovulation Induction
14.
Aust N Z J Obstet Gynaecol ; 61(4): 585-590, 2021 08.
Article in English | MEDLINE | ID: covidwho-1199633

ABSTRACT

BACKGROUND: In response to the COVID-19 pandemic in Australia, restrictions to elective surgeries were implemented nationwide. AIMS: To investigate the response to these restrictions in elective gynaecological and In vitro fertilisation (IVF) procedures during the first wave of the COVID-19 pandemic. MATERIALS AND METHODS: We analysed the Medicare Item Reports for the number of elective gynaecological (labioplasty, vulvoplasty; prolapse and continence; operative hysteroscopy; hysterectomy; fertility) and IVF procedures claimed in Australia between January-June 2020 and compared these to January-June 2019. RESULTS: The number of included gynaecological and IVF procedures performed in January-June 2020 decreased by -13.71% and -12.56%, respectively, compared to January-June 2019. The greatest reductions were in May 2020 (gynaecology -43.71%; IVF -51.63% compared to May 2019), while April 2020 reported decreases of -37.69% and -31.42% in gynaecological and IVF procedures, respectively. In April 2020, 1963 IVF cycle initiations (-45.20% compared to April 2019), 2453 oocyte retrievals (-26.99%) and 3136 embryo transfers (-22.95%) were billed. The procedures with greatest paired monthly decrease were prolapse and continence surgeries in April (676 procedures; -51.85%) and May 2020 (704 procedures; -60.05%), and oocyte retrievals in May 2020 (1637 procedures; -56.70%). CONCLUSIONS: While we observed a decrease in procedural volumes, elective gynaecological and IVF procedures continued in considerable numbers during the restricted timeframes. In the event of future overwhelming biological threat, careful consideration must be given to more effective measures of limiting access for non-emergency procedures to conserve essential resources and reduce risk to both the public and healthcare staff.


Subject(s)
COVID-19 , Gynecology , Aged , Female , Fertilization in Vitro , Humans , Medicare , Pandemics , SARS-CoV-2 , United States
15.
Reprod Biomed Online ; 42(6): 1067-1074, 2021 06.
Article in English | MEDLINE | ID: covidwho-1169278

ABSTRACT

RESEARCH QUESTION: Is there a risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral exposure and potential cross-contamination from follicular fluid, culture media and vitrification solution within the IVF laboratory using strict patient screening and safety measures? DESIGN: This was a prospective clinical study. All women undergoing transvaginal oocyte retrieval were required to have a negative SARS-CoV-2 RNA test 3-5 days prior to the procedure. Male partners were not tested. All cases used intracytoplasmic sperm injection (ICSI). The first tube of follicular fluid aspirated during oocyte retrieval, drops of media following removal of the embryos on day 5, and vitrification solution after blastocyst cryopreservation were analysed for SARS-CoV-2 RNA. RESULTS: In total, medium from 61 patients, vitrification solution from 200 patients and follicular fluid from 300 patients was analysed. All samples were negative for SARS-CoV-2 viral RNA. CONCLUSIONS: With stringent safety protocols in place, including testing of women and symptom-based screening of men, the presence of SARS-CoV-2 RNA was not detected in follicular fluid, medium or vitrification solution. This work demonstrates the possibility of implementing a rapid laboratory screening assay for SARS-CoV-2 and has implications for safe laboratory operations, including cryostorage recommendations.


Subject(s)
Culture Media/analysis , Fertilization in Vitro , Follicular Fluid/virology , Laboratories , RNA, Viral/isolation & purification , SARS-CoV-2/isolation & purification , Female , Humans , Oocyte Retrieval , Patient Safety , Prospective Studies , Sperm Injections, Intracytoplasmic , Vitrification
16.
JBRA Assist Reprod ; 25(2): 293-302, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1134427

ABSTRACT

COVID-19 has caused radical effects on the daily lives of millions of people. The causal agent of the current pandemic is SARS-CoV-2, a virus that causes symptoms related to the respiratory system, leading to severe complications. In the in vitro fertilization (IVF) universe, there are several protocols for infection control and laboratory safety. Some professional associations have issued guidelines recommending measures involving patient flow and IVF practices. This study presents a review and considerations for the resumption of activities in IVF laboratories and clinics in Brazil during the COVID-19 pandemic, according to the guidelines and statements from professional organizations and societies in reproductive medicine.


Subject(s)
Ambulatory Care Facilities/organization & administration , COVID-19 , Fertilization in Vitro , Infection Control , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , COVID-19/epidemiology , COVID-19/prevention & control , Child , Child, Preschool , Fertilization in Vitro/legislation & jurisprudence , Fertilization in Vitro/methods , Fertilization in Vitro/standards , Humans , Infant , Infection Control/legislation & jurisprudence , Infection Control/methods , Infection Control/standards , Laboratories/legislation & jurisprudence , Laboratories/standards , Middle Aged , Pandemics , SARS-CoV-2 , Young Adult
17.
J Assist Reprod Genet ; 38(6): 1449-1457, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1126571

ABSTRACT

PURPOSE: We aimed to assess whether home collection and increased time to semen processing are associated with altered sperm parameters, fertilization rates (FR), day 5 usable quality blastocyst development rates (D5-UQBR), or pregnancy rates (PR) in patients undergoing IVF/ICSI. METHODS: This was a retrospective cohort study of patients undergoing IVF/ICSI before the coronavirus disease 2019 (COVID-19) pandemic ("clinic" collection, n = 119) and after COVID-19 ("home" collection, n = 125) at an academic fertility practice. Home collection occurred within 2 h of semen processing. Patient sperm parameters, FR (#2PN/MII), D5-UQBR (# transferable and freezable quality blastocysts/# 2PN), and PR in fresh transfer cycles were compared between clinic and home groups with t-tests. The association between time to processing on outcomes was assessed with regression modeling, controlling for potential confounders. RESULTS: Mean male age was 37.9 years in the clinic group and 37.2 years in the home group (p = 0.380). On average, men were abstinent for 3.0 days (SD 1.7) in the clinic group and 4.1 days (SD 5.4) in the home group (p = 0.028). Mean time to semen processing was 35.7 min (SD 9.4) in the clinic group and 82.6 min (SD 33.8) in the home group (p < 0.001). There was no association between collection location and increased time to processing on sperm motility, total motile count, FR, D5-UQBR, or PR. CONCLUSIONS: Our data suggest that increased time to processing up to 2 h with home semen collection does not negatively impact sperm parameters or early IVF/ICSI outcomes.


Subject(s)
Blastocyst/cytology , Fertilization , Pregnancy Rate , Semen Preservation/methods , Semen , Spermatozoa/physiology , Adult , Ambulatory Care , COVID-19 , Embryo Transfer , Female , Fertilization in Vitro , Humans , Male , Outcome Assessment, Health Care , Pregnancy , Retrospective Studies , Semen Analysis , Sperm Injections, Intracytoplasmic , Sperm Motility , Time Factors
18.
Indian J Tuberc ; 67(4S): S111-S118, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1125083

ABSTRACT

Female genital tuberculosis (FGTB) is a common cause of infertility in India but its diagnosis remains elusive due to paucibacillary nature of disease. Traditional methods of diagnosis include demonstration of acid fast bacilli on endometrial or peritoneal biopsy or epithelioid granuloma on the biopsy or positive gene Xpert on the biopsy, but they are positive in small percentage of cases only missing diagnosis in many cases. Positive polymerase chain reaction (PCR) alone is not taken for diagnosis due to high false positivity. Diagnostic laparoscopy and hysteroscopy can detect many cases by direct demonstration of TB lesions. Composite reference standard is a useful method to diagnose FGTB. This review discusses various diagnostic modalities including endometrial or peritoneal biopsy to detect acid fast bacilli on microscopic or culture or epithelioid granuloma, role of PCR, role of radiological imaging (hysterosalpingography, ultrasound, CT scan, MRI and PET-CT scan) and role of endoscopic techniques (laparoscopy and hysteroscopy) in diagnosis of FGTB including role of composite reference standard. The International and National studies highlight the role of composite reference standard and its components like demonstration of AFB on microscopy or culture of endometrial or peritoneal biopsy or epithelioid granuloma or gene Xpert or PCR or latest tests like loop-mediated isothermal amplification (TB-LAMP) test and other newer molecular methods like Xpert Ultra for diagnosis of FGTB. It also detects role of endoscopy in FGTB and role of diagnostic algorithm for diagnosis of FGTB. Treatment is with four primary drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) for two months followed by three drugs (rifampicin, isoniazid and ethambutol) daily orally for 4 months for drug sensitive FGTB. Shorter Multidrug-resistant TB (MDR-TB) regimen is given for Rifampicin resistant (RR)/MDR confined to only FGTB while longer all oral regimen is given for RR/MDR with or without additional drug resistance, HIV seropositives with FGTB or involvement of other sites or pulmonary TB (PTB) along with FGTB. Composite reference standard which combines various diagnostic modalities is a useful strategy to diagnose FGTB.


Subject(s)
Tuberculosis, Female Genital/diagnosis , Algorithms , Antitubercular Agents/therapeutic use , Female , Fertilization in Vitro , Humans , India , Tuberculosis, Female Genital/drug therapy
19.
Hum Reprod ; 36(3): 666-675, 2021 02 18.
Article in English | MEDLINE | ID: covidwho-1096531

ABSTRACT

STUDY QUESTION: Can we use prediction modelling to estimate the impact of coronavirus disease 2019 (COVID 19) related delay in starting IVF or ICSI in different groups of women? SUMMARY ANSWER: Yes, using a combination of three different models we can predict the impact of delaying access to treatment by 6 and 12 months on the probability of conception leading to live birth in women of different age groups with different categories of infertility. WHAT IS KNOWN ALREADY: Increased age and duration of infertility can prejudice the chances of success following IVF, but couples with unexplained infertility have a chance of conceiving naturally without treatment whilst waiting for IVF. The worldwide suspension of IVF could lead to worse outcomes in couples awaiting treatment, but it is unclear to what extent this could affect individual couples based on age and cause of infertility. STUDY DESIGN, SIZE, DURATION: A population-based cohort study based on national data from all licensed clinics in the UK obtained from the Human Fertilisation and Embryology Authority Register. Linked data from 9589 women who underwent their first IVF or ICSI treatment in 2017 and consented to the use of their data for research were used to predict livebirth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three prediction models were used to estimate the chances of livebirth associated with immediate treatment versus a delay of 6 and 12 months in couples about to embark on IVF or ICSI. MAIN RESULTS AND THE ROLE OF CHANCE: We estimated that a 6-month delay would reduce IVF livebirths by 0.4%, 2.4%, 5.6%, 9.5% and 11.8% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, while corresponding values associated with a delay of 12 months were 0.9%, 4.9%, 11.9%, 18.8% and 22.4%, respectively. In women with known causes of infertility, worst case (best case) predicted chances of livebirth after a delay of 6 months followed by one complete IVF cycle in women aged <30, 30-35, 36-37, 38-39 and 40-42 years varied between 31.6% (35.0%), 29.0% (31.6%), 23.1% (25.2%), 17.2% (19.4%) and 10.3% (12.3%) for tubal infertility and 34.3% (39.2%), 31.6% (35.3%) 25.2% (28.5%) 18.3% (21.3%) and 11.3% (14.1%) for male factor infertility. The corresponding values in those treated immediately were 31.7%, 29.8%, 24.5%, 19.0% and 11.7% for tubal factor and 34.4%, 32.4%, 26.7%, 20.2% and 12.8% in male factor infertility. In women with unexplained infertility the predicted chances of livebirth after a delay of 6 months followed by one complete IVF cycle were 41.0%, 36.6%, 29.4%, 22.4% and 15.1% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, compared to 34.9%, 32.5%, 26.9%, 20.7% and 13.2% in similar groups of women treated without any delay. The additional waiting period, which provided more time for spontaneous conception, was predicted to increase the relative number of babies born by 17.5%, 12.6%, 9.1%, 8.4% and 13.8%, in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively. A 12-month delay showed a similar pattern in all subgroups. LIMITATIONS, REASONS FOR CAUTION: Major sources of uncertainty include the use of prediction models generated in different populations and the need for a number of assumptions. Although the models are validated and the bases for the assumptions are robust, it is impossible to eliminate the possibility of imprecision in our predictions. Therefore, our predicted live birth rates need to be validated in prospective studies to confirm their accuracy. WIDER IMPLICATIONS OF THE FINDINGS: A delay in starting IVF reduces success rates in all couples. For the first time, we have shown that while this results in fewer babies in older women and those with a known cause of infertility, it has a less detrimental effect on couples with unexplained infertility, some of whom conceive naturally whilst waiting for treatment. Post-COVID 19, clinics planning a phased return to normal clinical services should prioritize older women and those with a known cause of infertility. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, Merck KGaA, Guerbet and iGenomics. S.B. is Editor-in-Chief of Human Reproduction Open. None of the other authors declare any conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
COVID-19/epidemiology , Fertilization in Vitro , Health Priorities/organization & administration , Health Services Accessibility/organization & administration , Models, Organizational , Time-to-Treatment/organization & administration , Adult , Birth Rate , Cohort Studies , Datasets as Topic , Female , Humans , Live Birth/epidemiology , Male , Maternal Age , Pandemics , Pregnancy , Prospective Studies , SARS-CoV-2 , Time Factors , Time-to-Treatment/statistics & numerical data , United Kingdom/epidemiology
20.
BMJ Open ; 11(1): e042395, 2021 01 13.
Article in English | MEDLINE | ID: covidwho-1028310

ABSTRACT

INTRODUCTION: In vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen-thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited. METHODS AND ANALYSIS: We have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients' treatment burden. ETHICS AND DISSEMINATION: The study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL 6857).


Subject(s)
Birth Rate , Embryo Transfer , Blastocyst , Female , Fertilization in Vitro , Humans , Infant, Newborn , Live Birth , Multicenter Studies as Topic , Netherlands , Pregnancy , Pregnancy Rate , Randomized Controlled Trials as Topic
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