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Open access

B Karavadra, A Stockl, A H Balen, and E P Morris

Recently, fertility services have started resuming since COVID-19 was declared a pandemic, but there remains significant uncertainty in the way this care will be delivered in the United Kingdom. The objective of our study was to explore the impact of COVID-19 on individuals using fertility services in the United Kingdom. The study was conducted in two phases between May 2020 and July 2020: an online questionnaire involving 1212 participants and subsequent individual semi-structured telephone interviews with 15 participants. Through thematic analysis, we learned from the questionnaire findings that 74% of individuals identified as White British, 21% as Black and Minority Ethnic (BAME) and 2.6% as male. Ninety-six per cent of individuals from the questionnaire explained that COVID-19 had a ‘negative impact’ on their fertility treatment, namely ‘delay in care’. Eighty-two per cent of participants discussed concerns about the ‘uncertainty’ they felt about fertility services; these included the ‘unknown impact of COVID-19 on pregnancy outcomes’, the ‘unknown impact on general gynaecology services’ and the ‘unknown impact of COVID-19 on fertility success’. Through semi-structured telephone interviews with 15 participants, we learned about the ‘cultural pressures’ individuals from BAME backgrounds faced in relation to care. Participants were mindful about the ‘pressures on the service’ when reopening, and therefore ‘advancing maternal age’, ‘socio-economic background’ and ‘previous unsuccessful fertility treatment’ were the main factors individuals considered important when ‘prioritising’ fertility care. Our findings can be used by fertility service providers to appreciate the patient perspective when considering the reopening of fertility services nationally and internationally.

Lay summary

The impact of COVID-19 on patients seeking or undergoing fertility treatment is not entirely known. Many patients have had their treatment postponed during the pandemic. As fertility services begin to recommence, it is important to understand how the pandemic has affected this group of patients. In addition, it is vital to appreciate and understand the patient’s voice in order to ensure services take into account the patients’ concerns as they begin to offer certain fertility treatments. Our study was conducted in two phases and involved an online questionnaire and individual interviews with people. We found that people were worried about services restarting and how care would be prioritised. People also discussed some of the perceived barriers to seeking fertility healthcare. Our findings highlight the importance of understanding the patient’s voice when recommencing fertility services.

Open access

Dimitra Apostolia Androni, Sophie Dodds, Mathew Tomlinson, and Walid E Maalouf

Human sperm cryopreservation is characterised to this day by sub-optimal success rates. Interestingly, a traditional approach to improving post-thaw outcome has been to integrate standard sperm preparation techniques into freezing protocols as a means of selecting sperm with the highest fertilisation potential prior to insemination. However, no consensus has been reached yet regarding the optimal timing (before or after freezing) of this selection step. Following analysis of a total of 20 human semen samples, which were divided into two aliquots prepared by density gradient centrifugation either before or after freezing, this study demonstrated higher post-thaw total (P < 0.0001), progressively motile (P = 0.005) and vital (P < 0.0001) sperm counts for frozen-prepared semen samples. The present study suggests that direct insemination with frozen-prepared sperm with minimal intervening post-thaw processing might be a more advantageous approach to current clinical practices, particularly for donor and patient intrauterine insemination programmes. Further research into cryopreservation-induced coiled sperm tail morphology is also warranted.

Lay summary

Freezing and storing of sperm in liquid nitrogen (’sperm cryopreservation') is the current method of choice for preserving the fertility of a wide scope of men. Nevertheless, sub-optimal sperm survival is still associated with traditional cryopreservation methods, namely 'slow freezing', and may affect fertility treatment success rates. Interestingly, a widely applied approach for selecting high-quality sperm before treatment has been to incorporate 'sperm preparation' techniques, such as density gradient centrifugation, in slow freezing protocols. There is, however, an ongoing debate regarding which is the optimal timing of this selection step: before or after freezing. In this study, we collected 20 human semen samples which were divided into two portions and subjected to density gradient centrifugation either before or after freezing. Post-thaw semen analyses demonstrated significantly improved sperm counts (P < 0.05) when density gradient centrifugation was performed before freezing, thus suggesting this approach to be more advantageous for current clinical practices.

Open access

Bhorika Aggarwal, Amanda L Evans, Howard Ryan, and Sarah J Martins da Silva

Lay summary

In IVF, eggs and sperm are added together for fertilisation to occur whereas ICSI involves injecting a single sperm into each egg. ICSI is very effective where sperm count or swimming is poor (male infertility) but is slightly riskier than IVF in terms of health problems in children, although these risks are small. However, the risk of no eggs fertilising is higher for IVF compared to ICSI and couples undertaking fertility preservation, for example, before cancer treatment, usually only have time for one attempt. Using fertility preservation treatment cycle data reported to Human Fertilisation and Embryology Authority (HFEA), this study shows that ICSI results in higher number of fertilised eggs and embryos for storage or treatment compared to IVF. However, 19% of eggs are not used in ICSI treatment, so IVF appears to be better overall. Clinics should choose IVF or ICSI for fertility preservation depending on sperm characteristics rather than using ICSI for all.

Open access

Douglas A Gibson, Frances Collins, Bianca De Leo, Andrew W Horne, and Philippa T K Saunders

Endometriosis is a chronic neuroinflammatory pain condition affecting ~180 million women worldwide. Surgical removal or hormonal suppression of endometriosis lesions only relieves pain symptoms in some women and symptomatic relapse following treatment is common. Identifying factors that contribute to pain is key to developing new therapies. We collected peritoneal fluid samples and clinical data from a cohort of women receiving diagnostic laparoscopy for suspected endometriosis (n=52). Peritoneal fluid immune cells were analysed by flow cytometry and data compared with pain scores determined using the pain domain of the Endometriosis Health Profile Questionnaire (EHP-30) in order to investigate the association between peritoneal immune cells and pain symptoms. Pain scores were not different between women with or without endometriosis, nor did they differ according to disease stage; consistent with a poor association between disease presentation and pain symptoms. However, linear regression and correlation analysis demonstrated that peritoneal macrophage abundance correlated with severity of pelvic pain. CD14high peritoneal macrophages negatively correlated with pain scores whereas CD14low peritoneal macrophages were positively correlated, independent of diagnostic outcome at laparoscopy. Stratification by pain subtype, rather than endometriosis diagnosis, resulted in the most robust correlation between pain and macrophage adundance. Pain score strongly correlated with CD14high (p=0.007) and CD14low (p=0.008) macrophages in patients with non-menstrual pain and also in patients who reported dysmennorhea (CD14high p=0.021, CD14low p=0.019) or dysparunia (CD14high p=0.027, CD14low p=0.031). These results provide new insight into the association between peritoneal macrophages and pelvic pain which may aid identification of future therapeutic targets.

Open access

Liron Seidman, Daniella Gilboa, Polina Kimiagarov, Avia Noni, Ravid Doron, and Daniel S Seidman

objective: Oocyte pick-up (OPU) is a painful, but essential part of in-vitro fertilization (IVF) that is usually performed under sedation and analgesia (SaA). Our aim was to study why some women decide to undergo OPU without SaA?

methods: This was a prospective study using patient questionnaires and the standardized 7-item Generalized Anxiety Disorder (GAD-7) score. The patients were asked to assess the pain experienced during OPU using a Visual Analog Scale (VAS). The study sample was a convenience sample of 100 healthy women undergoing OPU at our unit with or without SaA.

Results: Women who chose to undergo OPU without SaA were significantly more likely to express fear of anesthesia. A high pain score (VAS≥6) was reported by significantly more patients who underwent OPU without SaA than with SaA. Yet, 98% of the patients who underwent OPU without SaA stated that in future IVF cycles, they would still choose to undergo OPU without SaA. More patients had high anxiety scores among those who underwent OPU with than without SaA.

Conclusions: Women who chose to undergo OPU without SaA reported more often fear of anesthesia. Although these women experienced significantly more pain during OPU, almost all of them suggested that they would still choose to undergo OPU without SaA. Increased anxiety, as expressed by higher GAD-7 scores, was not associated with a tendency to choose SaA during OPU. The option of OPU without SaA seems to be an acceptable option for selected women.

Open access

W Colin Duncan

The corpus luteum is the source of progesterone in the luteal phase of the cycle and the initial two-thirds of the first trimester of pregnancy. Normal luteal function is required for fertility and the maintenance of pregnancy. Progesterone administration is increasingly used during fertility treatments and in early pregnancy to mitigate potentially inadequate corpus luteum function. This commentary considers the concept of the inadequate corpus luteum and the role and effects of exogenous progesterone. Progesterone supplementation does have important beneficial effects but we should be wary of therapeutic administration beyond or outside the evidence base.

Lay summary

After an egg is released a structure is formed on the ovary called a corpus luteum (CL). This produces a huge amount of a hormone called progesterone. Progesterone makes the womb ready for pregnancy but if a pregnancy does not happen the CL disappears after 12–14 days and this causes a period. If a pregnancy occurs, then the pregnancy hormone (hCG) keeps the CL alive and its progesterone supports the pregnancy for the next 6–8 weeks until the placenta takes over and the corpus luteum disappears. That means that if the CL is not working correctly there could be problems getting pregnant or staying pregnant. If a CL is not producing enough progesterone it usually means there is a problem with the growing or releasing of the egg and treatment should focus on these areas. In IVF cycles, where normal hormones are switched off, the CL does not produce quite enough progesterone before the pregnancy test and extra progesterone is needed at this time. In recurrent or threatened miscarriage, however, there is not any evidence that the CL is not working well or progesterone is low. However, there is benefit in taking extra progesterone if there is bleeding in early pregnancy in women with previous miscarriages. This might be because of the effects of high-dose progesterone on the womb or immune system. As changes to the hormone environment in pregnancy may have some life-long consequences for the offspring we have to be careful only to give extra progesterone when we are sure it is needed.

Open access

Francesco Saverio Ludovichetti, Anna Giulia Signoriello, Edoardo Alvise Gobbato, Anna Artuso, Edoardo Stellini, and Sergio Mazzoleni

Today periodontal health is considered as an integral part of systemic health itself and no longer as a single factor. The literature recognizes that the presence of periodontal disease can represent a risk factor for numerous systemic conditions such as heart disease and diabetes. In recent years, we have witnessed a progressive interest regarding the influence exerted by this condition on reproduction, as well as the possible repercussions on conception possibilities. Upon analyzing a limited number of studies available for the correlation between periodontal disease and female infertility, it could be inferred that this condition can be equated to the presence of a real outbreak of infection and therefore exert its influence, not only through bacterial translocation in the bloodstream, causing the systemic dissemination of pathogens, but also through the production of cytokines and immunoglobulins by inflammatory mediators. This situation limits bacterial growth, but it could cause damage to the fetus, to the reproductive system, and could hinder conception attempts. Although further research is needed to better clarify the mechanism underlying the possible correlation between periodontal disease and female infertility, the present article aims to review all the available literature on this topic.

Lay summary

In recent years, interest regarding the influence of gum disease on conception has increased. Since serious gum disease (periodontitis) can be compared to an outbreak of infection, studies suggest that the bacteria that mediate inflammation do not remain confined only to the gum tissue, but can enter the bloodstream and spread, thus spreading the infection and having a whole-body effect. This situation could cause damage to the developing baby, to the reproductive system and could hinder conception attempts. Constant maintenance of oral health is definitely necessary. It is important for the professionals involved (gynecologists, obstetricians, dentists, etc.) to communicate and collaborate on these issues. Dentists could advise on the correct hygienic maintenance not only to pregnant women, but also to those who are planning a pregnancy in order to avoid the occurrence of unfavorable conditions.

Open access

Briet D Bjarkadottir, Charlotte A Walker, Muhammad Fatum, Sheila Lane, and Suzannah Alice Williams

In vitro follicle growth is a potential fertility preservation method for patients for whom current methods are contraindicated. Currently this method has only been successful using fresh ovarian tissue. Since many patients who may benefit from this treatment currently have cryopreserved ovarian tissue in storage, optimising in vitro follicle growth (IVG) for cryopreserved-thawed tissue is critical. This study sought to improve the first step of IVG by comparing different short-term culture systems for cryopreserved-thawed human ovarian tissue, in order to yield a higher number of healthy multilayer follicles. We compared two commonly used culture media (αMEM and McCoy’s 5A), and three plate conditions (300 µL, 1 mL on a polycarbonate membrane and 1 mL in a gas-permeable plate) on the health and development of follicles after six days of culture. A total of 5,797 follicles from three post-pubertal patients (aged 21.3 ± 2.3 years) were analysed across six different culture conditions and non-cultured control. All culture systems supported follicle development and there was no difference in developmental progression between the different conditions tested. Differences in follicle morphology were evident with follicles cultured in low volume conditions having significantly greater odds of being graded as morphologically normal compared to other conditions. Furthermore, culture in a low volume of αMEM resulted in the highest proportion of morphologically normal primary and multilayer follicles (23.8% compared to 6.3-19.9% depending on condition). We therefore recommend culture of cryopreserved human ovarian tissue in a low volume of αMEM to support follicle health and development.

Open access

Elis Torrezan-Nitao, Hector Guidobaldi, Laura Giojalas, Christopher Barratt, and Stephen Publicover

Repetitive [Ca2+]i transients (oscillations), observed in progesterone (P4)-stimulated immobilised human sperm, reversibly modifiy flagellar beating. Here we report that such oscillations also occur in P4-stimulated free-swimming sperm and regulate (or contribute to) behavioural switching.

Open access

Megan Brown, Mick Rae, and Nick Wheelhouse

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