Influence of Caesarean section–pregnancy interval on uterine rupture risk and IVF pregnancy rates: systematic review and mathematical modelling
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?
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.
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.
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.
The success rate of IVF has significantly improved over the last decade
Jessica J. Wade, Vivien MacLachlan, Gab Kovacs
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.
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.
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.
Cumulative success rates following mild IVF in unselected infertile patients: a 3-year, single-centre cohort study
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.
Cryopreserved oocytes: update on clinical applications and success rates.
Paramanantham J, Talmor AJ, Osianlis T, Weston GC.
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.
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.
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.
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.
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.
This review will be relevant to clinicians interested in fertility treatments using cryopreserved oocytes, fertility preservation, oncology and fertility, and immunology and fertility.
In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43
Hsiao-Ling Lee , David H. McCulloh, Brooke Hodes-Wertz, et al.
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.
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.
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.
The present data provides evidence of the benefits of PGS with regard to improved implantation and live birth rate per embryo transferred.
Effect of male and female body mass index on pregnancy and live birth success after in vitro fertilization
Karen C. Schliep, Sunni L. Mumford, Ph.D.a, Katherine A. Ahrens, et al.
To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes.
Prospective cohort study.
University fertility center.
All couples undergoing first fresh IVF cycles, 2005–2010, for whom male and female weight and height information were available (n = 721 couples).
Main Outcome Measure(s)
Embryologic parameters, clinical pregnancy, and live birth incidence.
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.
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.
A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria
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.