Oocyte retrieval, a pivotal step in the in vitro fertilization (IVF) process, involves the collection of mature oocytes from the ovaries through ultrasound-directed transvaginal follicle aspiration. Despite its efficacy, this procedure often induces pain and stress, necessitating exploration into various pain relief options.

Conscious sedation, a widely used approach involving a combination of sedatives and local anesthetics, allows patients to remain conscious while minimizing discomfort during the procedure. It has minimal side effects and is low risk, facilitating a swift return to normal activities and early discharge. However, some patients still endure pain and discomfort, leading to the investigation of additional techniques for enhanced comfort and satisfaction. Moreover, it is recognized that a patient’s psychological state has an influence on sedation. Patients experiencing anxiety may require higher sedative doses, posing challenges for clinicians. Recognising the influence of a patient’s mental health, research on non-pharmacological methods to reduce anxiety and improve sedation experience expanding.

Sedation by virtual reality (VR) has been emerging as an innovative method for relieving patients’ pain and anxiety throughout medical procedures. This transformative digital therapy employs three-dimensional multi-sensory immersion, combining clinical hypnotherapy and integrative therapeutics. By stimulating multiple human senses, VR systems create an immersive experience, fostering a feeling of presence in the virtual world. Although the positive psychological impact of VR on sedation outcomes is increasingly being acknowledged, limited research has explored the benefits of VR, specifically hypnosis, in the field of fertility during surgical interventions such as oocyte retrieval.
The preliminary data collected aimed to investigate the anxiety-reducing effects and patient satisfaction associated with VR during oocyte retrieval, focusing on its potential as an alternative to traditional analgesics.

A total of forty patients undergoing oocyte retrieval consented to participate in the VR experience, facilitated through an immersion headset. The VR session commenced, lasting a maximum of 20 minutes. Low doses of fentanyl (75mcg) and midazolam (1mg) were administered as needed, with sedation adjusted to ensure patient comfort. Subsequently, each participant completed a comprehensive questionnaire before discharge, providing insights into pain perception, overall experience, and satisfaction levels.

Results from the questionnaire suggest this non-pharmacological approach is effective and has a positive impact on patient well-being. Notably, 63% of participants reported a high level of immersion during the VR session, while, 95% of patients noted an additional level of comfort during the oocyte retrieval procedure. The most striking statistic was the satisfaction category, with 98% expressing high levels of contentment with the VR session.

A subgroup analysis involved patients with prior oocyte retrieval experience. In this cohort, 93% declared that VR significantly improved their comfort levels during the procedure. Additionally, an equivalent percentage acknowledged an overall enhancement in their experience of the oocyte retrieval process.

In conclusion, the integration of VR in a clinical setting emerges as a promising approach complementing routine sedation, with a notable level of patient adherence. The high satisfaction reported by participants underscores its potential as an easily implementable solution within a clinical setting, offering tangible improvements in patient comfort during oocyte retrieval. These results warrant further investigation through prospective multi-centre studies involving larger cohorts. Such studies are essential to solidify the efficacy of pain management using VR devices in reproductive medicine practice. The future integration of these innovative technologies holds the promise of revolutionizing and elevating the overall patient experience in fertility treatments.

Based on: https://www.focusonreproduction.eu/article/News-in-Reproduction-VR-in-oocyte-retrieval

Why isn’t this treatment more accessible?

Have you heard about platelet-rich plasma or PRP? Neither have I. It’s a treatment that’s been around for years. Simply and relatively effective, its application is more widely known in the world of sports. History dates this treatment back to the 1970s where it was used in a study around wound healing. The 1980s showed PRP application in the dental field, followed by its application in orthopaedics and sports injuries in the 1990s.

So how does it work?

There’s four parts to our blood:

• Plasma: made up of 90% water, this is the liquid component to our blood,
• Platelets: smaller cell fragments that help with blood clots,
• White blood cells: help us fight infections and injuries, and
• Red blood cells: transport oxygen.

For women with low ovarian reserve who are trying to conceive, this could mean a significant decrease in assisted reproductive technology (ART) costs with an increase in conception success rates. Although the study was limited to those who have been trying for less than 3 years, intraovarian PRP injections could be a game changer. As concluded in this 2023 study from a team based out of Romania: “PRP administration seems to improve implantation, clinical pregnancy, chemical pregnancy, on-going pregnancy, live birth rates, and endometrial thickness in women with previous implantation failure.”

Wider application for women

The application of PRP treatment is helping women in a wide variety of use cases:

• High-risk women after Caesarean section showed faster wound healing times using this more therapeutic approach.
• Improving menstruation recovery rates of 60% of women had POI or poor ovarian response, 40% of menopausal women positively responded to PRP treatment and 80% of perimenopausal women had menstruation regularity.
• Patients with vesicovaginal fistula, the communication between the bladder and vagina, benefited from PRP injections during and after their Latzko procedure. “In all cases, the vaginal wall at the site of the procedure healed without any signs of scarring, redness, or granulosa tissue. Moreover, patients did not complain about any urination difficulties or urinary tract disorders.”

Based on: https://www.sunnysidebump.com/blog/this-plasma-treatment-is-increasing-the-ivf-odds-by-3x

According to the authors of a large retrospective cohort study (1) which has found that the fertility treatment offers no benefit over conventional IVF (cIVF) for embryo quality and live birth rates (LBRs).

Based on more than 30,000 PGT-A cycles carried out in the USA for non-male factor infertility, the main findings show that embryos suitable for transfer and LBRs ‘are not significantly different’ in cIVF vs ICSI. In addition, ICSI did not improve secondary outcomes such as gestational age at delivery, birth weight and unexplained infertility.

The study which used data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SARS CORS) adds to the debate around the overuse of ICSI outside its primary indication for male infertility. While acknowledging that ICSI has enabled ‘countless’ infertile men to have genetically-related children, the authors say the fertility treatment is ‘not without its limitations’ including increased cost and controversy over adverse neonatal outcomes.

The use of ICSI for PGT-A has arisen out of concerns that results could be affected by contamination from residual cumulus cells and from surplus sperm attached to the zona pellucida because of cIVF. On this basis, ESHRE good practice recommendations have suggested ICSI is preferable for PGT (2) as have those from the American Society of Reproductive Medicine (ASRM) (3).

However, the authors of this retrospective cohort study say that advancements in PGT-A mean genomic contamination has been ‘drastically reduced’. They say this calls into question ‘the necessity of ICSI for PGT-A tested embryos ’, a conclusion which has been backed up by other studies. Moreover, the authors argue that the use cIVF for non-male factor PGT-A cycles could lead to a decrease in costs and in ‘embryology labor’ for fertility clinics. The results also question clinics’ rising use of ICSI for unexplained fertility in the belief that couples will benefit by increasing their chance of having a baby.

The authors used data from the SART CORS database) relating to all cIVF/ICSI cycles involving PGT-A from January 2014 to December 2017. SART CORS holds information from fertility clinics in the USA who are SART members. All frozen thawed embryo transfer (FET) cycles linked to PGT-A cycles were also evaluated for LBRs.

The primary outcomes were percentage of embryos suitable for transfer and LBRs. Secondary outcomes included subgroup analysis for embryos suitable for transfer on cycles from patients aged 35 years (y/o) or above vs those aged under 35 years; 6 or fewer oocytes retrieved vs more than 6; and cycles with the diagnosis of unexplained infertility. Additionally, gestational age at delivery and birthweight between cIVF and ICSI were evaluated.

Additional secondary outcomes included rates of pregnancy loss, average gestational age at delivery, birthweight, and sub-analysis of first FET cycles.

Exclusion criteria included PGT cycles where either parent was a carrier for a genetic disease, use of frozen oocytes and cycles with more than 10 embryos biopsied; and potential confounding variables included maternal age, maximum FSH level and number of oocytes retrieved.

A total of 30,446 non-male factor PGT-A cycles (n=4,867 cIVF cycles; n=25,579 ICSI) met the inclusion criteria. Results showed no significant differences in rate of embryos suitable for transfer between cIVF vs ICSI (41.6% vs 42.5% respectively, p=0.12) or within the patient subgroups (≥35 y/o=35.7% vs 36.5%, p=0.25; <35 y/o=57.6% vs 58.6%, p=0.21; ≤6 oocytes retrieved=32.9% vs 35.3%, p=0.12; >6 oocytes retrieved=43.9% vs 44.2%, p=0.66; and unexplained infertility=46.4% vs 48.8%, p=0.09).

Analysis of single FET (n=3,412 IVF; n=16,358 ICSI) found no significant differences for LBRs (50.1% vs 50.8% respectively, p=0.51) and pregnancy loss rates (16.6% vs 15.5, p=0.11); and sub-analysis of first FET transfers only in cIVF vs ICSI revealed a similar trend for LBRs (53.4% vs 53%, p=0.78) and pregnancy loss rates (15.7% vs 15.5%, p=0.84).

In addition, no significant differences were found in cIVF vs ICSI for gestational age in days (265.8 vs 265.6, p=0.73) and birth weight in grams at delivery (3,376.7 vs 3,363.5, p value=0.42).

Limitations of the study include the fact data may be biased towards larger centres, and that ICSI requires technical skill which may differ among embryologists and between centres.

Several areas of research were not covered by this SART CORs analysis: these are recommended for further study by the authors. In their paper, they write that evaluation of the incidence of mosaic embryos is important ‘given the ability’ for these embryos to lead to live births; and suggest that evidence is needed on whether ICSI decreases paternal contamination during PGT-A cycles.

References:
1 Tozour J, Arnott A, Akerman M, Sung L, Vintzileos A and Fritz R. Comparison of Outcomes Between Intracytoplasmic Sperm Injection and In Vitro Fertilization with Pre-implantation Genetic Testing for Aneuploidy, Analysis of SART CORS Data. Fertility and Sterility (2024); https://doi.org/10.1016/j.fertnstert.2023.12.041
2 Georgia Kokkali et al. ESHRE PGT Consortium and SIG-Embryology Biopsy Working Group. ESHRE PGT Consortium and SIG Embryology good practice recommendations for polar body and embryo biopsy for PGT. HR Open 2020 (3); https://doi.org/10.1093/hropen/hoaa020
3 Intracytoplasmic sperm injection (ICSI) for non–male factor indications: a committee opinion Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Fert and Steril 2020; vol 114 (2); https://doi.org/10.1016/j.fertnstert.2020.05.032

Roberto Matorrasa, Leire Berreteagaa, Lucía Laínzb, et al.

Research question

What is the influence of the Caesarean section–pregnancy interval (CSPI) on the risk of uterine rupture, and what are the repercussions on IVF pregnancy rates of prolonging it?

Study design

Systematic searches were performed using PubMed MEDLINE to identify studies published up until July 2017 for articles with the following keywords: ‘interdelivery interval’ and ‘uterine rupture’; ‘interpregnancy interval’ and ‘uterine rupture’; ‘interpregnancy interval’ and ‘cesarean section’; and ‘uterine rupture’ and ‘cesarean section’. The search identified 1609 articles, of which six were included (involving 56,419 women). Four reported significantly higher uterine rupture rates in cases of a short CSPI.

Results

From the analysis, the uterine rupture rate can be modelled by a formula corresponding to a hyperbolic curve. There is no clear cut-off in uterine rupture in relation to CSPI. The curve showed a sharp decrease in uterine rupture until the 10th month of CSPI (uterine rupture rate 0.7%), then a moderate and steady decrease until the 40th month (uterine rupture rate 0.4%) and afterwards a very mild decrease. From the data it is possible to calculate, according to the age of the woman, the expected reduction in IVF rates and uterine rupture as CSPI increases.

Conclusion

The risk of uterine rupture in relation to CSPI can be represented by means of a hyperbolic curve. After a 10-month CSPI, the expected uterine rupture rate is close to 0.7%. The impact of prolonging or reducing this interval on IVF pregnancy rates can be easily obtained from the table included in the article. This should be helpful in the decision-making process for both patients and physicians. https://www.rbmojournal.com/article/S1472-6483(19)30660-1/fulltext

Jessica J. Wade, Vivien MacLachlan, Gab Kovacs

Aim

To demonstrate that success rates with in vitro fertilisation (IVF) have been improving despite decreasing the number of embryos transferred.

Materials and Methods

This was a retrospective cohort study comparing live birth outcomes for women who started IVF between 2001 and 2005 with women who started between 2006 and 2010, using life table analysis to allow for the fact that women had differing number of cycles of treatment. The data were obtained from a single IVF centre, Monash IVF Geelong, Victoria. The 2001–2005 cohort consisted of 233 women, and the 2006–2010 cohort consisted of 453 women who started IVF between the specified dates. The main outcome measure was a live birth. Life table analysis was used to estimate the cumulative probability of a live birth after each cycle.

Results

The estimate of cumulative live birth probability demonstrated that the chance of a live birth by cycle five was 75.8% in the 2001–2005 cohort, which significantly increased to 80.1% by cycle five in the 2006–2010 cohort (P = <0.05). There was a mean of 1.8 embryos transferred per embryo transfer in the 2001–2005 cohort, which decreased to a mean of 1.3 embryos transferred per embryo transfer in the 2006–2010 cohort. This was associated with a significant decrease in the multiple birth rate from 24.7% in the 2001–2005 cohort to 7.5% in the 2006–2010 cohort.

Conclusion

The IVF success rate has significantly improved despite the number of embryos transferred being reduced. This study provides further support for elective single embryo transfers.

http://onlinelibrary.wiley.com/doi/10.1111/ajo.12356/abstract

Daniel Bodria, Satoshi Kawachiyaa, Michaël De Bruckerb, et al.

A 3-year, retrospective, single-centre cohort study was conducted in a private infertility centre to determine cumulative live birth rates (LBR) per scheduled oocyte retrieval following minimal ovarian stimulation/natural-cycle IVF in unselected infertile patients. A total of 727 consecutive infertile patients were analysed who underwent 2876 (median 4) cycles with scheduled oocyte retrieval from November 2008 to December 2011. Natural-cycle IVF or clomiphene-based minimal ovarian stimulation was coupled with single-embryo transfer and increased use of delayed vitrified–warmed blastocyst transfer. Main outcome measures were crude and expected age-specific cumulative LBR per scheduled oocyte retrieval. Crude cumulative LBR were 65%, 60%, 39%, 15% and 5% in patients aged 26–34, 35–37, 38–40, 41–42 and 43–44 years, respectively. No live births occurred in patients aged ⩾45 years. Dropout rates per cycle were 13–25%. Success rates gradually reached a plateau, with few additional live births after six cycles. Most of the expected success rate was reached within 6 months with almost maximal rates within 15 months of the first oocyte retrieval. Acceptable cumulative LBR are reached with an exclusive minimal ovarian stimulation/single-embryo transfer policy especially in patients aged <38 years but also in intermediate aged patients (38–40 years).

A 3-year, retrospective, single-centre cohort study was conducted in a private infertility centre to determine the cumulative delivery rates following minimal ovarian stimulation/natural-cycle IVF in unselected infertile patients. A total of 727 consecutive infertile patients were analysed who underwent 2876 treatment cycles (median four) with scheduled oocyte retrieval from November 2008 to December 2011. Natural-cycle IVF or clomiphene-based minimal ovarian stimulation was coupled with a universal single-embryo transfer policy and increased use of delayed cryopreserved blastocyst transfer. Main outcome measures were crude and expected age-specific cumulative delivery rates. Crude cumulative live birth rates were 65%, 60%, 39%, 15% and 5% in patients aged 26–34, 35–37, 38–40, 41–42 and 43–44 years, respectively. No live births occurred in patients aged ⩾45 years. Dropout rates per cycle varied between 13% and 25%. A plateau in success rates was reached gradually with few additional live births after six cycles. Most of the expected success rate was reached within 6 months, with almost maximal rates within 15 months of the first oocyte retrieval. Acceptable cumulative live birth rates are reached with an exclusive minimal ovarian stimulation/single-embryo transfer policy especially in patients aged <38 years.http://www.sciencedirect.com/science/article/pii/S1472648314000546

Paramanantham J, Talmor AJ, Osianlis T, Weston GC.

IMPORTANCE:

Over the past 3 decades, oocyte cryopreservation procedures have improved rapidly. However, there is limited research reviewing the efficacy of different cooling protocols and inadequate data comparing in vitro fertilization (IVF) outcomes from fresh oocytes with cryopreserved oocytes.

OBJECTIVE:

The present review was performed to investigate advances in oocyte cryopreservation technologies and identify areas for further research, to determine whether results from IVF using cryopreserved oocytes are comparable to IVF using fresh oocytes, and to identify the patient populations requiring access to oocyte cryopreservation.

EVIDENCE ACQUISITION:

A literature review was conducted. OVID (MEDLINE) and PubMed databases were queried using phrases such as «oocyte or egg» and «cryopreservation,» «vitrification,» or «slow cooling or slow freezing.» A total of 180 studies were selected for review.

RESULTS:

Current literature suggests that vitrified oocytes produce superior IVF results to slow-frozen oocytes and may yield comparable outcomes to IVF with fresh oocytes in certain patient populations. Patients at risk of infertility due to disease or age-related decline or oocyte donation programs, couples who fail to produce semen when required for IVF, and patients with legal or ethical reasons against embryo cryopreservation may access cryopreserved oocytes.

CONCLUSIONS:

We suggest that women who comprise the previously mentioned patient populations should be offered oocyte vitrification technology. Further research is required to confirm IVF success across all patient populations and determine the best cryopreservation protocols.

RELEVANCE:

This review will be relevant to clinicians interested in fertility treatments using cryopreserved oocytes, fertility preservation, oncology and fertility, and immunology and fertility.

http://www.ncbi.nlm.nih.gov/pubmed/25671372

Hsiao-Ling Lee , David H. McCulloh, Brooke Hodes-Wertz, et al.

Purpose

In Vitro Fertilization is an effective treatment for infertility; however, it has relatively low success in women of advanced maternal age (>37) who have a high risk of producing aneuploid embryos, resulting in implantation failure, a higher rate of miscarriage or birth of a child with chromosome abnormalities. The purpose of this study was to compare the implantation, miscarriage and live birth rates with and without preimplantation genetic screening (PGS) of embryos from patients aged 40 through 43 years.

Methods

This is a retrospective cohort study, comparing embryos screened for ploidy using trophectoderm biopsy and array comparative genomic hybridization to embryos that were not screened. We compared pregnancy outcomes for traditional fresh IVF cycles with day 5 embryo transfers, Frozen Embryo Transfer (FET) cycles without PGS and PGS-FET (FET of only euploid embryos) cycles of patients with maternal ages ranging from 40 to 43 years, undergoing oocyte retrievals during the period between 1/1/2011 and 12/31/2012.

Results

The implantation rate of euploid embryos transferred in FET cycles (50.9 %) was significantly greater than for unscreened embryos transferred in either fresh (23.8 %) or FET (25.4 %) cycles. The incidence of live birth per transferred embryo for PGS-FET (45.5 %) was significantly greater than for No PGS fresh (15.8 %) or No PGS FET (19.0 %) cycles. The incidences of live birth per implanted sac for PGS FET cycles (89.3 %), No PGS fresh cycles (66.7 %) and No PGS FET cycles (75.0 %) were not significantly different.

Conclusions

The present data provides evidence of the benefits of PGS with regard to improved implantation and live birth rate per embryo transferred.

http://link.springer.com/article/10.1007%2Fs10815-014-0417-7

Karen C. Schliep, Sunni L. Mumford, Ph.D.a, Katherine A. Ahrens, et al.

Objective

To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes.

Design

Prospective cohort study.

Setting

University fertility center.

Patient(s)

All couples undergoing first fresh IVF cycles, 2005–2010, for whom male and female weight and height information were available (n = 721 couples).

Intervention(s)

None.

Main Outcome Measure(s)

Embryologic parameters, clinical pregnancy, and live birth incidence.

Result(s)

The average male BMI among the study population was 27.5 ± 4.8 kg/m² (range, 17.3–49.3 kg/m²), while the average female BMI (n = 721) was 25.2 ± 5.9 kg/m² (range, 16.2–50.7 kg/m²). Neither male nor female overweight (25–29.9 kg/m²), class I obese (30–34.9 kg/m²), or class II/III obese (≥35 kg/m²) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5–24.9 kg/m²) status after adjusting for male and female age, partner BMI, and parity. Similar null findings were found between combined couple BMI categories and IVF success.

Conclusion(s)

Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed.

http://www.sciencedirect.com/science/article/pii/S0015028214023085

Andrea Busnelli, Enrico Papaleo, Diana Del Prato, et al.

STUDY QUESTION Do the Bologna criteria for poor responders successfully identify women with poor IVF outcome?

SUMMARY ANSWER The Bologna criteria effectively identify a population with a uniformly low chance of success.

WHAT IS ALREADY KNOWN Women undergoing IVF who respond poorly to ovarian hyper-stimulation have a low chance of success. Even if improving IVF outcome in this population represents a main priority, the lack of a unique definition of the condition has hampered research in this area. To overcome this impediment, a recent expert meeting in Bologna proposed a new definition of poor responders (‘Bologna criteria’). However, data supporting the relevance of this definition in clinical practice are scanty.

STUDY DESIGN, SIZE, DURATION Retrospective study of women undergoing IVF-ICSI between January 2010 and December 2012 in two independent infertility units. Women could be included if they fulfilled the definition of poor ovarian response (POR) according to Bologna criteria prior to initiation of the cycle. Women were included only for one cycle. The main outcome was the live birth rate per started cycle. The perspective of the cost analysis was the one of the health provider.

PARTICIPANTS/MATERIALS, SETTING, METHODS Three-hundred sixty-two women from two independent Infertility Units were selected. A binomial distribution model was used to calculate the 95% CI of the rate of success. Characteristics of women who did and did not obtain a live birth were compared. A logistic regression model was used to adjust for confounders. The economic analysis included costs for pharmacological compounds and for the IVF procedure. The benefits were estimated on quality-adjusted life years (QALY). To develop the model, we used the local life-expectancy tables, we applied a 3% discount of life years gained and we used a 0.07 improvement in quality of life associated with parenthood. Sensitivity analyses were performed varying the improvement of the quality of life and including/excluding the male partner. The reference values for cost-effectiveness were the Italian and the local (Lombardy) gross domestic product (GDP) pro capita per year in the studied period and the upper and lower limits suggested by NICE.

MAIN RESULTS AND THE ROLE OF CHANCE Overall, 23 women had a live birth (6%, 95% CI: 4–9%), in line with the previous evidence. This proportion did not significantly differ in the different subgroups of poor responders. Positive predictive factors of success were previous deliveries (adjusted OR = 3.0, 95% CI: 1.1–8.7, P = 0.039) and previous chemotherapy (adjusted OR = 13.9, 95% CI: 2.5–77.2, P = 0.003). Age, serum AMH, serum FSH and antral follicle count were not significantly associated with live birth. The total cost per live birth was 87 748 Euros, corresponding to 49 919 Euros per QALY. This is above both the limits suggested by NICE for cost-effectiveness and the Italian and local GDP pro capita. Sensitivity analyses mainly support the robustness of the conclusion.

LIMITATIONS, REASONS FOR CAUTION We lack a control group and we cannot thus exclude that an alternative definition of poor responders may be equally if not more valid. Moreover, independent validations are warranted prior to concluding that IVF is not cost-effective. Women should thus not be denied treatment based on our findings. Noteworthy, there is also not yet a consensus on the most appropriate economic model to be used.

WIDER IMPLICATIONS OF THE FINDINGS We recommend the use of the Bologna criteria when designing future studies on poor responders. Large multi-centred international studies are now required to draw definite conclusions on the economic profile of IVF in this situation.

STUDY FUNDING/COMPETING INTERESTS None.

TRIAL REGISTRATION NUMBER Not applicable.http://humrep.oxfordjournals.org/content/30/2/315.abstract