Recent Submissions

  • The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET).

    Melo, Pedro; Wood, Simon; Petsas, Georgios; Chung, Yealin; Easter, Christina; Price, Malcolm J; Fishel, Simon; Khairy, Mohammed; Kingsland, Charles; Lowe, Philip; et al. (Oxford University Press, 2022-11-28)
    Study question: What is the association between serum progesterone levels on the day of frozen embryo transfer (FET) and the probability of live birth in women undergoing different FET regimens? Summary answer: Overall, serum progesterone levels <7.8 ng/ml were associated with reduced odds of live birth, although the association between serum progesterone levels and the probability of live birth appeared to vary according to the route of progesterone administration. What is known already: Progesterone is essential for pregnancy success. A recent systematic review showed that in FET cycles using vaginal progesterone for endometrial preparation, lower serum progesterone levels (<10 ng/ml) were associated with a reduction in live birth rates and higher chance of miscarriage. However, there was uncertainty about the association between serum progesterone levels and treatment outcomes in natural cycle FET (NC-FET) and HRT-FET using non-vaginal routes of progesterone administration. Study design size duration: This was a multicentre (n = 8) prospective cohort study conducted in the UK between January 2020 and February 2021. Participants/materials setting methods: We included women having NC-FET or HRT-FET treatment with progesterone administration by any available route. Women underwent venepuncture on the day of embryo transfer. Participants and clinical personnel were blinded to the serum progesterone levels. We conducted unadjusted and multivariable logistic regression analyses to investigate the association between serum progesterone levels on the day of FET and treatment outcomes according to the type of cycle and route of exogenous progesterone administration. Our primary outcome was the live birth rate per participant. Main results and the role of chance: We studied a total of 402 women. The mean (SD) serum progesterone level was 14.9 (7.5) ng/ml. Overall, the mean adjusted probability of live birth increased non-linearly from 37.6% (95% CI 26.3-48.9%) to 45.5% (95% CI 32.1-58.9%) as serum progesterone rose between the 10th (7.8 ng/ml) and 90th (24.0 ng/ml) centiles. In comparison to participants whose serum progesterone level was ≥7.8 ng/ml, those with lower progesterone (<7.8 ng/ml, 10th centile) experienced fewer live births (28.2% versus 40.0%, adjusted odds ratio [aOR] 0.41, 95% CI 0.18-0.91, P = 0.028), lower odds of clinical pregnancy (30.8% versus 45.1%, aOR 0.36, 95% CI 0.16-0.79, P = 0.011) and a trend towards increased odds of miscarriage (42.1% versus 28.7%, aOR 2.58, 95% CI 0.88-7.62, P = 0.086). In women receiving vaginal progesterone, the mean adjusted probability of live birth increased as serum progesterone levels rose, whereas women having exclusively subcutaneous progesterone experienced a reduction in the mean probability of live birth as progesterone levels rose beyond 16.3 ng/ml. The combination of vaginal and subcutaneous routes appeared to exert little impact upon the mean probability of live birth in relation to serum progesterone levels. Limitations reasons for caution: The final sample size was smaller than originally planned, although our study was adequately powered to confidently identify a difference in live birth between optimal and inadequate progesterone levels. Furthermore, our cohort did not include women receiving oral or rectal progestogens. Wider implications of the findings: Our results corroborate existing evidence suggesting that lower serum progesterone levels hinder FET success. However, the relationship between serum progesterone and the probability of live birth appears to be non-linear in women receiving exclusively subcutaneous progesterone, suggesting that in this subgroup of women, high serum progesterone may also be detrimental to treatment success. Study funding/competing interests: This work was supported by CARE Fertility and a doctoral research fellowship (awarded to P.M.) by the Tommy's Charity and the University of Birmingham. M.J.P. is supported by the NIHR Birmingham Biomedical Research Centre. S.F. is a minor shareholder of CARE Fertility but has no financial or other interest with progesterone testing or manufacturing companies. P.L. reports personal fees from Pharmasure, outside the submitted work. G.P. reports personal fees from Besins Healthcare, outside the submitted work. M.W. reports personal fees from Ferring Pharmaceuticals, outside the submitted work. The remaining authors have no conflict of interest to declare. Trial registration number: ClinicalTrials.gov: NCT04170517.
  • Chromosomal polymorphisms in assisted reproduction: an analysis of 942 cycles

    Ralapanawe, Madara S B; Gajaweera, Sugandika Lakmali; Karunaratne, Nishendra; Price, Malcolm James; Melo, Pedro; Coomarasamy, Arri; Gallos, Ioannis (BioScientifica, 2022-08-01)
    The use of intracytoplasmic sperm injection (ICSI) has recently increased worldwide. The live birth rate per ICSI cycle is low, and over half of infertile couples remain childless. Chromosomal polymorphisms are up to five times more common in couples with infertility compared to the general population. We aimed to investigate the association between chromosomal polymorphisms and reproductive outcomes in couples undergoing ICSI treatment. We analysed 942 ICSI fresh and frozen embryo transfer cycles in 697 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman banding prior to assisted conception at the Fertility Centre of Lanka Hospitals, Sri Lanka, between 2016 and 2018. The primary outcomes were pregnancy, miscarriage, and live birth rates. We compared outcomes according to the presence or absence of chromosomal polymorphism in females, males and couples. There were 294 pregnancies (31.2%) recorded in the study; 130 suffered a miscarriage (13.8%), 13 were ectopic pregnancies (1.3%) and 151 resulted in a live birth (16.0%). The evidence from univariable and multivariable analyses (adjusted for age, BMI, ovarian reserve and treatment type) did not confidently identify a difference in pregnancy, miscarriage or live birth rates between couples with no chromosomal polymorphisms compared to couples where the female, male or both partners were carriers of a chromosomal polymorphism. Further, we did not identify a clear association between the presence of chromosomal polymorphisms and reproductive outcomes compared to participants without chromosomal polymorphisms. Wide CIs precluded the identification of clinically meaningful associations. Lay summary: Infertility affects approximately one in eight couples worldwide. The use of intracytoplasmic sperm injection (ICSI), where the sperm is directly injected into an egg using a micromanipulator outside the body, has become particularly popular in recent years. However, the success rate remains low. In human cells, the genetic material is arranged in structures called chromosomes. Chromosomal polymorphism is a normal variation where the genetic material is arranged differently to the average individual and is more common in infertile couples compared to the general population. We analysed data from 942 ICSI cycles in 697 couples who underwent karyotyping analysis to assess the changes in chromosomes between 2016 and 2018. The pregnancy rate was 31.2%, with 16.0% of participants experiencing a live birth, while 13.8% of pregnancies resulted in a miscarriage and 1.3% were outside the womb cavity (ectopic). The evidence did not identify a clear association between the chromosomal polymorphism and the outcome of treatment.
  • Author correction: A comprehensive analysis of chromosomal polymorphic variants on reproductive outcomes after intracytoplasmic sperm injection treatment.

    Ralapanawe, Madara S B; Gajaweera, Sugandika L; Karunaratne, Nishendra; Dissanayake, Vajira H W; Price, Malcolm J; Melo, Pedro; Coomarasamy, Arri; Gallos, Ioannis D (Nature Publishing Group, 2023-06-21)
    No abstract available
  • Body image concerns in women with polycystic ovary syndrome: a systematic review and meta-analysis

    Davitadze, Meri; Malhotra, Kashish; Khalil, Halimah; Hebbar, Meghnaa; Tay, Chau Thien; Mousa, Aya; Teede, Helena; Brennan, Leah; Stener-Victorin, Elisabet; Kempegowda, Punith; et al. (Oxford University Press, 2023-08-02)
    Objective: To assess differences in body image concerns among women with and without polycystic ovary syndrome (PCOS). Design: This is a systematic review and meta-analysis. Methods: Electronic databases (MEDLINE, EMBASE, APA PsychInfo, PUBMED, Web-of-Science Core Collection, and Cochrane Controlled Register of Trials [CENTRAL]) were searched from inception through July 2022. Outcome measures included validated questionnaires reporting on body image concerns. Methodological quality was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system, and included studies were assessed for risk of bias. Meta-analyses were performed using the inverse variance method based on random or fixed effects models (Review Manager, Version 5). Results: A total of 918 women with PCOS and 865 women without PCOS from 9 studies were included. Meta-analysis of 3 studies using Multidimensional Body-Self Relations Questionnaire Appearance Scale (MBSRQ-AS) showed those with PCOS reported higher dissatisfaction with appearance evaluation and appearance orientation compared to those without PCOS (mean difference [MD] = -0.78, I2 = 0%, P < .00001, and MD = 0.22, I2 = 54%, P = .004, respectively). Meta-analysis of 2 studies showed higher dissatisfaction with overweight preoccupation, lower body area satisfaction, and body weight classification on MBSRQ-AS subscales in those with PCOS compared to those without PCOS (all P < .001). Meta-analysis of 2 studies using the Body Esteem Scale for Adolescents and Adults (BESAA) showed significantly lower scores for the weight subscale in those with PCOS compared to those without PCOS (P = .03). Conclusions: Those with PCOS experience more significant body image concerns, emphasising the importance of awareness in the clinical care of PCOS. Considering the limited evidence, further studies are warranted to identify drivers and mitigating factors.
  • Experiences of young girls and women undergoing ovarian tissue cryopreservation: a systematic review and thematic synthesis.

    Khattak, Hajra; Woodman, Hannah; Afifi, Yousri; Amorim, Christiani A; Fishel, Simon; Gallos, Ioannis; Coomarasamy, Arri; Topping, Annie; Topping, Annie; Nursing; et al. (Taylor and Francis Group, 2022-07-04)
    The aim of this study was to explore the experiences of young girls and women who underwent or considered ovarian tissue cryopreservation (OTC) using a systematic review of qualitative studies with thematic synthesis framework. Major electronic databases: MEDLINE, EMBASE, the Cochrane Library, CINAHL and PsycINFO were searched from 1946 to May 2020 and reference lists of relevant articles were hand searched. Any studies that described a qualitative inquiry and highlighted the experiences of women with regards to OTC were included. Two independent reviewers screened the title and abstracts and made a selection against inclusion criteria. Main outcomes measures were experiences of women who have considered and/or undergone OTC, decision making in women who underwent or considered OTC and patient education. Nineteen studies were assessed for full text eligibility and four were included in analysis. 144 verbatim quotations from 85 participants in high income countries (UK, USA and Denmark) were included. Two studies adopted grounded theory approach, one phenomenology and one inductive content analysis. Four themes were generated; participants described their experiences as emotional, involving complex decision-making, helping them prepare for the long-term consequences of potentially losing their fertility and hormonal function, as well as their experience being educational. Additionally, the more practical aspects of the procedure such as OTC being invasive as well as costs implications were highlighted. Women and young girls are often involved in making time-sensitive decisions whether or not to undergo OTC. Healthcare professionals involved in the care of young girls and women undergoing this method need to also take into consideration the emotional wellbeing of the patients as well as the time and expertise it requires to help them make an informed decision.