STUDY QUESTION

Are alterations in decidual expression of interleukin (IL)-6 and IL-8 associated with sporadic miscarriage?

SUMMARY ANSWER

IL-6 and IL-8 secretion from decidual uterine natural killer (uNK) cells and macrophages isolated from women with spontaneous miscarriage was reduced compared with normal controls.

WHAT IS KNOWN ALREADY

Miscarriage is a common gynaecological problem with huge financial and personal implications. Eleven to twenty per cent of all clinically recognized pregnancies are lost before the 20th week of gestation, with miscarriages often being divided into early (≤12 completed weeks from last menstrual period) and late (≥13 weeks). Spiral artery remodelling is a key feature of early pregnancy; failure of this process has been implicated in sporadic miscarriage. The molecular triggers that initiate spiral artery remodelling are not clear, although cytokines such as IL-6 and IL-8 may play a role.

STUDY DESIGN, SIZE, DURATION

This was a laboratory-based study using decidual and placental bed biopsy samples from women with sporadic miscarriage (n = 30) and termination of pregnancy controls (n = 30).

PARTICIPANTS/MATERIALS, SETTING, METHODS

Total adherent decidual cells, CD10⁺ stromal cells, CD14⁺ macrophages and CD56⁺ uNK cells were isolated from decidua from apparently normal pregnancies that were terminated at either 8–10 or 12–14 weeks' gestation. In addition, CD14⁺ macrophages and CD56⁺ uNK cells were isolated from decidua from sporadic miscarriage at 8–10 weeks' gestation. Secreted IL-8 was measured in all isolated cell populations, while IL-6 was measured in CD14⁺ macrophages and CD56⁺ uNK cells from both sporadic miscarriage and normal controls. Placental bed biopsies were taken from women after sporadic miscarriage or termination of pregnancy at ≤12 completed weeks' or >13 weeks' gestational age, formalin-fixed, paraffin-embedded and immunostained for IL-6, IL-6Rα, GP130, IL-8, CXCR1, CXCR2 and CD13 (aminopeptidase N). Staining intensity for each factor was assessed in extravillous trophoblast cell populations, myometrial and decidual stroma, myometrial and decidual spiral arteries and decidual glandular epithelium. A CPA model was used to assess the potential role of IL-6 and IL-8 in spiral artery remodelling.

MAIN RESULTS AND THE ROLE OF CHANCE

IL-8 was secreted by total adherent decidual cells, CD10⁺ stromal cells and CD14⁺ macrophages at both 8–10 and 12–14 weeks' gestation, with CD14⁺ cells secreting the highest levels. Both CD14⁺ and CD56⁺ cells isolated from decidua of early sporadic miscarriage produced lower IL-6 (P = 0.04, P = 0.01, respectively) and IL-8 levels (P = 0.0007, P = 0.002, respectively) compared with normal cases. In addition, altered expression of IL-6, IL-8 and their receptors was observed in various cell types in placental bed (myometrial stroma, glandular epithelium, interstitial extravillous trophoblast cells, vascular smooth muscle cells and endothelial cells) in sporadic miscarriage, particularly from later gestational ages. IL-6 and IL-8 disrupted vascular smooth muscle morphology and organization in an in vitro model of spiral artery remodelling.

LIMITATIONS, REASONS FOR CAUTION

By the nature of sampling at the time of miscarriage, it was not possible to ascertain the cause or effect in the observed alterations of levels of IL-6 and IL-8 in sporadic miscarriage.

WIDER IMPLICATIONS OF THE FINDINGS

Alterations in the expression of IL-6, IL-8 and their receptors may be associated with the aetiology of sporadic miscarriage, especially given the potential role of these cytokines in the regulation of trophoblast invasion and spiral artery remodelling.

STUDY FUNDING/COMPETING INTEREST(S)

This project was supported by funding from Wellbeing of Women (RG1000). The authors have no competing interests to declare.

TRIAL REGISTRATION NUMBER

Not applicable.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2075?rss=1

STUDY QUESTION

How does vitrification affect oocyte viability?

SUMMARY ANSWER

Vitrification does not affect oocyte viability in oocyte donation cycles.

WHAT IS KNOWN ALREADY

Oocyte vitrification is performed routinely and successfully in IVF and oocyte donation programs.

STUDY DESIGN, SIZE, DURATION

This is a prospective study performed between June 2009 and February 2012 to compare ongoing pregnancy rates and other indices of viability between fresh and vitrified oocytes. A total of 99 donations with more than 16 oocytes (MII) in which oocytes were allocated both to a synchronous recipient (fresh oocytes) and to an asynchronous recipient (vitrified oocytes) were included.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The participants were consenting couples (donors and recipients) from the oocyte donation program. On the day of retrieval, the oocytes allocated to the synchronous recipient were inseminated and those allocated for banking were denuded of cumulus and vitrified. Vitrified oocytes were microinjected with spermatozoa 2 h after warming. Embryo transfer was performed on Day 2 of development in both groups, and the remaining embryos were cryopreserved on Day 3. Clinical pregnancy was defined by a positive fetal heartbeat at 6 weeks.

MAIN RESULTS AND ROLE OF CHANCE

A total of 989 oocytes were warmed and 85.6% survived. No significant differences were observed between fresh and vitrified oocytes: fertilization rate (80.7 versus 78.2%), ongoing embryo rate (71.0 versus 68.2%) or good-quality embryo rate (54.1 versus 49.8%). The mean number of embryos transferred was similar in both groups (1.82 ± 0.44 versus 1.90 ± 0.34). The implantation rate (33.3 versus 34.0%) and the multiple pregnancy rate (27.7 versus 20.8) were also similar between both groups (P > 0.05). The live birth rate per cycle was 38.4% in the recipients of fresh oocytes and 43.4% in the recipients of vitrified oocytes (P > 0.05). Eighty five frozen embryo transfers were also evaluated. Comparing embryos from fresh and vitrified oocytes there were no significant differences in the embryo survival rate (70.1 versus 65.8%), clinical pregnancy rate (40.8 versus 33.3%) or implantation rate (21.8 versus 26.8%).

LIMITATIONS, REASONS FOR CAUTION

The oocytes were donated by healthy, young women (≤35 years) and these results cannot be extrapolated to other populations.

WIDER IMPLICATIONS OF THE FINDINGS

Outcomes obtained with vitrified oocytes are as good as with fresh oocytes and the use of vitrification can be extended to new applications, e.g. accumulation of oocytes from successive stimulations for preimplantation genetic diagnosis, for patients at risk of ovarian hyperstimulation syndrome or in patients needing to preserve their fertility.

STUDY FUNDING/COMPETING INTEREST(S)

This work was done under the auspices of the Càtedra d'Investigació en Obstetrícia i Ginecologia of the Universitat Autònoma de Barcelona.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2087?rss=1

STUDY QUESTION

Does vitrification and warming of Day 3 embryos have an impact on neonatal outcome when compared with Day 3 embryos that are slow cooled and thawed, or with embryos from a fresh cycle?

SUMMARY ANSWER

The median birthweight was higher in the vitrified group versus the slow cooled or fresh embryo transfer, and the rate of low birthweight in twin babies was lower in the vitrified group.

WHAT IS KNOWN ALREADY

Vitrification has been successfully used for cryopreserving human oocytes and blastocyst-stage embryos. Most published studies looking at the neonatal outcomes after transfer of vitrified embryos refer to blastocyst-stage embryos. Information on children born after transfer of Day 3 vitrified embryos is relatively rare.

STUDY DESIGN, SIZE, DURATION

A retrospective, single-centre study of children born after Day 3 embryo transfer from fresh, slow frozen or vitrified embryos during the period January 2006 to May 2011 was conducted. Each patient contributed only one cycle per group. Children born were followed-up at 7–30 days after delivery. Outcome measures include obstetric and neonatal outcomes, which were evaluated by medical records and questionnaires sent to parents.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Patients underwent transfer of vitrified Day 3 embryos (n = 2617 transfers, Cryotop method), slow frozen Day 3 embryos (n = 4681) and fresh Day 3 embryos (n = 9194). All cycles were performed at the Shanghai Ji Ai Genetics & IVF Institute.

MAIN RESULTS AND THE ROLE OF CHANCE

Frequencies of hypertensive disorder, gestational diabetes, placenta previa and abruptio placenta were similar in all groups. Five hundred and forty five, 986 and 1914 singleton babies were born from vitrified, slow freezing and fresh transfers, and the median gestational ages were 38.7, 38.7 and 38.7 weeks, respectively. Preterm birth (32–37 weeks) occurred in 7.5, 9.2 and 7.8% of the vitrified, slow freeze and fresh groups, respectively. The median birthweight from vitrified embryos (3455.3 g) was higher than that from slow freezing (3352.3 g) and fresh (3355.8 g) transfers (P < 0.0001 for both). The rate of perinatal mortality was 0.4% for all transfer groups. Three hundred and eighty two, 734 and 1322 twin babies were born from vitrified, slow freezing and fresh transfers, respectively. There were no differences among groups in mean gestational age and in the rate of preterm birth. The median birthweight for babies born from vitrified embryos (2587.4 g) was higher than that from the slow freezing (2538.8 g) or fresh (2494.4 g) transfer groups (vitrified versus fresh: P = 0.0015; vitrified versus slow freeze: P = 0.049). The rate of low birthweight (1500–2500 g) from vitrified (30.4%) was lower than that from fresh (36.2%) transfer (P = 0.034).

LIMITATIONS, REASONS FOR CAUTION

The main limitation of this study is that the obstetric and neonatal data were obtained by questionnaires sent to the parents without checking medical records. This is, especially, problematic for reporting on congenital malformations, so birth defects were excluded from the data.

WIDER IMPLICATIONS OF THE FINDINGS

Transfer of vitrified and warmed Day 3 embryos does not seem to have an adverse effect on neonatal outcome. Children born following the transfer of vitrified embryos seem to have a higher birthweight when compared with those of fresh or slow frozen embryos.

STUDY FUNDING/COMPETING INTEREST(S)

This study received no outside funding and none of the authors has any conflict of interest.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2093?rss=1

STUDY QUESTION

What is the intracellular concentration of cryoprotectant (ICCP) in mouse zygotes during vitrification (VIT) and slow-freezing (SLF) cryopreservation procedures?

SUMMARY ANSWER

Contrary to common beliefs, it was observed that the ICCP in vitrified zygotes is lower than after SLF, although the solutions used in VIT contain higher concentrations of cryoprotectants (CPs).

WHAT IS KNOWN ALREADY

To reduce the likelihood of intracellular ice crystal formation, which has detrimental effects on cell organelles and membranes, VIT was introduced as an alternative to SLF to cryopreserve embryos and gametes. Combined with high cooling and warming rates, the use of high concentrations of CPs favours an intracellular environment that supports and maintains the transition from a liquid to a solid glass-like state devoid of crystals. Although the up-to-date publications are reassuring in terms of obstetric and perinatal outcomes after VIT, a fear about exposing gametes and embryos to high amounts of CPs that exceed 3–4-fold those found in SLF was central to a debate initiated by advocates of SLF procedures.

STUDY DESIGN, SIZE, DURATION

Two experimental set-ups were applied. The objective of a first study was to determine the ICCP at the end of the exposure steps to the CP solutions with our VIT protocol (n = 31). The goal of the second investigation was to compare the ICCP between VIT (n = 30) and SLF (n = 30). All experiments were performed in triplicates using mouse zygotes. The study took place at the GIGA-Research Institute of the University of Liège.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Cell volume is modified by changes in extracellular osmolarity. Hence, we estimated the final ICCP after the incubation steps in the VIT solutions by exposing the cells to sucrose (SUC) solutions with defined molarities. The ICCP was calculated from the SUC concentration that produced no change in cell volume, i.e. when intra- and extracellular osmolarities were equivalent. Cell volume was monitored by microscopic cinematography. ICCP was compared between SLF and VIT based on the principle that a high ICCP lowers the probability of (re)crystallization during warming but increases the probability of over-swelling of the cell due to fast inflow of water. The survival rates of mouse zygotes after SLF or VIT were compared using either (i) various warming rates or (ii) various concentrations of SUC in the warming dilution medium.

MAIN RESULTS AND THE ROLE OF CHANCE

The ICCP in mouse zygotes during the VIT procedure prior to plunging them in liquid nitrogen was ~2.14 M, i.e. one-third of the concentration in the VIT solution. After SLF, the warming rate did not affect the zygote survival rate. In contrast, only 3/30 vitrified zygotes survived when warmed slowly but as many as 30/30 zygotes survived when warming was fast (>20 000°C/min). Vitrified zygotes showed significantly higher survival rates than slow-frozen zygotes when they were placed directly in the culture medium or in solutions containing low concentrations of SUC (P < 0.01). These two experiments demonstrate a lower ICCP after VIT than after SLF.

LIMITATIONS, REASONS FOR CAUTION

The results should not be directly extrapolated to other stages of development or to other species due to possible differences in membrane permeability to water and CPs.

WIDER IMPLICATIONS OF THE FINDINGS

The low ICCP we observed after VIT removes the concern about high ICCP after VIT, at least in murine zygotes and helps to explain the observed efficiency and lack of toxicity of VIT.

STUDY FUNDING / COMPETING INTEREST(S)

The study was funded by the FNRS (National Funds for Scientific Research). The authors declare that they have no competing interests.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2101?rss=1

STUDY QUESTION

Should oocytes showing the presence of smooth endoplasmic reticulum aggregates (SER) be considered for embryo transfer?

SUMMARY ANSWER

The present study shows that embryos derived from metaphase II oocyte with visible SER (SER+MII) have the capacity to develop normally and may lead to newborns with no major malformations.

WHAT IS KNOWN ALREADY

It has been reported that the presence of SER in the cytoplasm of oocytes has a negative impact on embryo development, and is associated with a decreased clinical outcome and an increased risk of congenital anomalies. Therefore, it has been recommended that embryos derived from SER-positive oocytes should not be transferred.

STUDY DESIGN, SIZE, DURATION

Consecutive ICSI cycles with at least one SER+MII oocyte were retrospectively analyzed regarding embryological and pregnancy outcome and compared with ICSI cycles showing only oocytes without SER (SER–MII).

PARTICIPANTS/MATERIALS, SETTING, METHODS

In total, 394 SER-positive (SER+) cycles and 6845 SER-negative (SER–) cycles were analyzed. The Student's t-test, one-way analysis of variance test and ² test were used for statistical analysis. P value of <0.05 was considered statistically significant.

MAIN RESULTS AND THE ROLE OF CHANCE

Comparable fertilization rates were observed in SER+ (76.2%) and SER– (73.5%) cycles. In case of blastocyst culture, the cycle efficiency was lower in SER+ than in SER– cycles (mean 42.2 versus 62.8%, P < 0.001). The pregnancy and clinical pregnancy (CP) rates per embryo transfer (ET) were comparable for SER+ and SER– cycles (37.6 versus 37.8% and 33.0 versus 32.4%, respectively).

In the SER+ cycles, the fertilization rates of SER+MII and SER–MII (72.9 versus 77.0%), as well as the capacity to develop into good-quality embryos on Days 3 (62.3 versus 63.7%) and 5 (45.4 versus 47.4%), were similar. In the 364 SER+ cycles, the ETs were subdivided in: ET with only SER+MII (n = 31; 8.5%), ET with only SER–MII (n = 235; 64.5%) and ET with mixed SER+ and SER–MII (n = 98; 26.9%). The pregnancy (25.8, 37.4 and 41.8%, respectively) and CP rates (22.6, 32.4 and 37.9%, respectively) were not different between the three subgroups. Among the cycles with known outcome, there was no difference in the rate of major malformations between SER+ cycles (5.3%) and SER– cycles (2.1%). Moreover, no major malformations were reported from the live borns definitely originating from SER+MII embryos. In addition, three newborns, from single ET with frozen–thawed embryos originating from SER+MII oocytes, were delivered and presented no major malformation.

LIMITATIONS, REASONS FOR CAUTION

Taking into account the previous publications and our neonatal data, a follow-up of the children born after ET with embryos originating from SER+ cycles is encouraged.

WIDER IMPLICATION OF THE FINDINGS

More studies should be performed to investigate the origin and effect of SER aggregates on the molecular status of oocytes and embryos.

STUDY FUNDING/COMPETING INTEREST(S)

No external funding was either sought or obtained for this study and there are no potential competing interests.

TRIAL REGISTRATION NUMBER

Not applicable.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2111?rss=1

STUDY QUESTION

How effective is the vaginal administration of misoprostol in dilating the cervix prior to inserting an intrauterine device (IUD) in nulligravidas?

SUMMARY ANSWER

The use of misoprostol at a dose of 400 µg administered vaginally 4 h prior to IUD insertion increased the ease of insertion and reduced the incidence of pain during the procedure, although the frequency of cramps increased following misoprostol use.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

Misoprostol has been widely used in Obstetrics and Gynecology; however, its usefulness and efficacy in facilitating IUD insertion in nulligravidas have yet to be established. The present study shows that the benefits of misoprostol use prior to IUD insertion include facilitating insertion and reducing pain during the procedure; therefore, weighing up the benefits encountered against the only negative side effect (cramps prior to insertion), these results suggest that misoprostol use should become standard practice to facilitate IUD insertion in nulligravidas.

STUDY DESIGN, SIZE DURATION

A randomized, double-blind clinical trial was conducted.

PARTICIPANTS/MATERIALS, SETTING METHODS

Nulligravid women of reproductive age were submitted to IUD insertion between July 2009 and November 2011 at the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, Brazil. A total of 179 women were randomly allocated to two groups: 86 to receive 400 µg of misoprostol vaginally 4 h prior to IUD insertion and 93 to receive placebo. Risk ratios (RRs) were calculated as measures of relative risk, together with their 95% confidence intervals (95% CI). The number needed to treat (NNT) and the number needed to harm (NNH) were also calculated.

MAIN RESULTS AND THE ROLE OF CHANCE

Significant differences were found between the groups for all the immediate end points studied, with less difficulty in inserting the IUD [RR = 0.49 (23/86 versus 51/93); 95% CI: 0.33–0.72; P = 0.00005], a lower risk of dilatation <4 mm [RR = 0.48 (24/86 versus 54/93); 95% CI: 0.33–0.70; P = 0.0001], a reduction in moderate-to-severe pain at IUD insertion [RR = 0.56 (32/86 versus 62/93]; 95% CI: 0.41–0.76; P = 0.00008), as well as a lesser likelihood of experiencing a disagreeable or very disagreeable sensation [RR = 0.49(29/86 versus 64/93); 95% CI: 0.35–0.68; P = 0.000004] in the group that was given misoprostol compared with the group that received placebo. There was no significant difference between the groups in relation to complications during IUD insertion. There were no cases of uterine perforation in either group. The frequency of cramps was 40% higher in the misoprostol group.

LIMITATIONS, REASONS FOR CAUTION

The present study showed a positive balance between the benefits and risks of the use of misoprostol; however, it is not feasible to conclude that its use is imperative prior to IUD insertion in nulligravidas and IUD insertion should not be canceled when the medication is unavailable.

WINDER IMPLICATIONS OF THE FINDINGS

In view of its effect in promoting cervical dilatation, misoprostol may be used prior to IUD insertion both in nulligravidas and in any women with cervical stenosis irrespective of parity.

STUDY FUNDING

This study was funded by the Instituto de Medicina Integral Prof Fernando Figueira.

COMPETING INTERESTS

None.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2118?rss=1

STUDY QUESTION

Are interleukin-33 (IL-33) serum levels higher in women with uterine leiomyoma compared with controls without leiomyoma?

SUMMARY ANSWER

Serum IL-33 is elevated in women with uterine leiomyoma and correlated with features of uterine leiomyoma tumour burden, namely fibroid number, size and weight.

WHAT IS KNOWN ALREADY

Uterine leiomyomas are the most common benign tumours in premenopausal women associated with major tissue fibrosis. IL-33 is a cytokine involved in fibrotic disorders. The potential role of IL-33 in leiomyoma has not been reported before.

STUDY DESIGN, SIZE, DURATION

This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2005 and December 2010. We investigated non-pregnant, 42-year-old patients (n = 151) during surgery for a benign gynaecological condition.

PARTICIPANTS/MATERIALS, SETTING, METHODS

After complete surgical exploration of the abdominopelvic cavity, 59 women with histologically proved uterine leiomyoma and 92 leiomyoma-free control women were enrolled. Women with endometriosis or past history of ovarian malignancy and borderline tumours were not included. The control group included women with benign ovarian cysts, paratubal cysts or tubal defects without any evidence of uterine leiomyoma. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. Serum samples were obtained in the month preceding the surgical procedures according to the menstrual phase or hormonal therapy. IL-33 was measured in sera by enzyme-linked immunosorbent assay, and correlation of IL-33 concentration with the extent and severity of the disease was investigated.

MAIN RESULTS AND THE ROLE OF CHANCE

IL-33 was detected in 32 (54.2%) women with leiomyoma and 18 (19.6%) controls (P < 0.001). Serum IL-33 was higher in women with leiomyoma (median, 140.1 pg/ml; range, 7.5–2247.7) than in controls (median, 27.8 pg/ml; range, 7.5–71.6; P = 0.002). We found positive correlations between serum IL-33 concentration and leiomyoma features, such as fibroid weight (r = 0.630; P = 0.001) and size (r = 0.511; P = 0.018) and the number of fibroids (r = 0.503; P = 0.003).

LIMITATIONS, REASONS FOR CAUTION

There was a possible selection bias due to inclusion of only surgical patients. Therefore our control group consisted of women who underwent surgery for benign gynaecological conditions. This may lead to biases stemming from the fact that certain of these conditions, such as tubal infertility or ovarian cysts, might be associated with altered serum IL-33 levels.

WIDER IMPLICATIONS OF THE FINDINGS

We demonstrate for the first time that elevated serum IL-33 levels are associated with the existence of uterine leiomyoma. However, even if an association does not constitute proof of cause and effect, investigating the mechanisms that underlie fibrogenesis associated with leiomyomas is a step towards understanding this enigmatic disease. This study opens the doors to future, more mechanistics studies to establish the exact role of IL-33 in uterine leiomyomas pathogenesis.

STUDY FUNDING/COMPETING INTEREST(S)

No funding, no conflict of interest.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2126?rss=1

STUDY QUESTION

Does fallopian tube sperm perfusion (FSP) result in better pregnancy and live birth rates than standard intrauterine insemination (SIUI) for couples with non-tubal infertility with or without gonadotrophin or clomiphene stimulation?

SUMMARY ANSWER

There was no evidence of an improvement in live birth rates with FSP compared with SIUI.

WHAT IS KNOWN ALREADY

Previous randomized controlled trials have suggested improved live birth rates with FSP but these trials were small. A systematic review published in 2004 suggested heterogeneity in results.

STUDY DESIGN, SIZE, AND DURATION

This pragmatic, multicentre, randomized controlled trial compared SIUI and FSP in 417 women with non-tubal infertility.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The patients were treated at fertility clinics in New Zealand, Australia and the United Arab Emirates.

MAIN RESULTS AND THE ROLE OF CHANCE

Four hundred and seventeen women were randomized to SIUI (n = 210) or FSP (n = 207). Data were available for analysis from 198 women in the SIUI group and 198 women in the FSP group. There were 19 women with incomplete data because of cycle cancellation or withdrawals and 2 women who conceived prior to commencing treatment. There were no significant differences in live birth rates between the two groups with 27 (12.9%) in the SIUI group and 21 in the FSP group (10.1%) [Odds Ratio (OR) 1.31 (0.71, 2.39), P = 0.48]. Two ectopic pregnancies were reported in the SIUI group and one was reported in the FSP group.

LIMITATIONS, REASONS FOR CAUTION

Different ovulation protocols were used in the different clinics. Approximately 10% of the cycles involved donor sperm and ~5% of the cycles did not complete the assigned intervention.

WIDER IMPLICATIONS OF THE FINDINGS

There was no evidence of an improvement in live birth rates with FSP compared with SIUI.

STUDY FUNDING/COMPETING INTEREST(S)

The study was funded in part by the A+ trust of the Auckland District Health Board. No commercial funding was received.

TRIAL REGISTRATION NUMBER

ANZCTR Number ACTRN12612001303831.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2134?rss=1

STUDY QUESTION

Do the presence of endometriomas and their laparoscopic excision lead to a decrease in ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) levels?

SUMMARY ANSWER

Both the presence and excision of endometriomas cause a significant decrease in serum AMH levels, which is sustained 6 months after surgery.

WHAT IS KNOWN ALREADY

No previous comparison of serum AMH levels between women with and without endometrioma has been reported. However, studies have suggested a decline in serum AMH levels 1–3 months after endometrioma excision but long-term data are needed.

STUDY DESIGN, SIZE, DURATION

A prospective cohort study including 30 women with endometrioma >2 cm were age matched with 30 healthy women without ovarian cysts.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Women with endometrioma underwent laparoscopic excision with the stripping technique. Serum AMH level and antral follicle count (AFC) were determined preoperatively, 1 and 6 months after surgery. Correlation analyses were undertaken in order to identify determinants of surgery-related change in ovarian reserve.

MAIN RESULTS AND THE ROLE OF CHANCE

Compared with controls at baseline, women with endometrioma had lower AMH levels (4.2 ± 2.3 versus 2.8 ± 2.2 ng/ml, respectively, P = 0.02) and AFC (14.7 ± 4.1 versus 9.7 ± 4.8, respectively, P < 0.01). Serum AMH levels were further decreased 6 months after surgery (2.8 ± 2.2 versus 1.8 ± 1.3 ng/ml, P = 0.02), while AFC remained unchanged (9.7 ± 4.8 versus 10.4 ± 4.2, P = 0.63). The rate of decline in AMH was not correlated with age, laterality of endometrioma, cyst diameter or the number of primordial follicles on the surgical specimens. The preoperative serum AMH level was positively correlated with the rate of decline in serum AMH after surgery (r = 0.47, P = 0.02).

LIMITATIONS, REASONS FOR CAUTION

The absence of a non-treated group of women with endometriomas as a further control prevents comment on the presence of a progressive decline in ovarian reserve related to endometrioma per se. The sample size may be too small for detection of factors correlated with the extent of ovarian damage.

WIDER IMPLICATIONS OF THE FINDINGS

While the findings are mostly in agreement with previous studies, the present study is the first to show that the presence of endometrioma per se is associated with a decrease in ovarian reserve. The extent of surgery-related decline in ovarian reserve is not predictable using preoperative or perioperative factors. It may be prudent to measure AMH levels preoperatively and delay/avoid surgical excision as far as is possible if subsequent fertility is a concern. Additional studies are required to further investigate whether the endometrioma-related decline in ovarian reserve per se is progressive in nature and whether it exceeds the surgery-related decline.

STUDY FUNDING/COMPETING INTEREST(S)

This study was funded by the Research Fund of the Uludag University School of Medicine. The authors have no conflict of interest associated with this study.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2140?rss=1

STUDY QUESTION

Can a vitrification protocol using an ethylene glycol/dimethyl sulphoxide-based solution and a cryopin successfully cryopreserve baboon ovarian tissue?

SUMMARY ANSWER

Our results show that baboon ovarian tissue can be successfully cryopreserved with our vitrification protocol.

WHAT IS KNOWN ALREADY

Non-human primates have already been used as an animal model to test vitrification protocols for human ovarian tissue cryopreservation.

STUDY DESIGN, SIZE, DURATION

Ovarian biopsies from five adult baboons were vitrified, warmed and autografted for 5 months.

PARTICIPANTS/MATERIALS, SETTING, METHODS

After grafting, follicle survival, growth and function and also the quality of stromal tissue were assessed histologically and by immunohistochemistry. The influence of the vitrification procedure on the cooling rate was evaluated by a computer model.

MAIN RESULTS

After vitrification, warming and long-term grafting, follicles were able to grow and maintain their function, as illustrated by Ki67, anti-Müllerian hormone (AMH) and growth differentiation factor-9 (GDF-9) immunostaining. Corpora lutea were also observed, evidencing successful ovulation in all the animals. Stromal tissue quality did not appear to be negatively affected by our cryopreservation procedure, as demonstrated by vascularization and proportions of fibrotic areas, which were similar to those found in fresh ungrafted ovarian tissue.

LIMITATIONS, REASONS FOR CAUTION

Despite our promising findings, before applying this technique in a clinical setting, we need to validate it by achieving pregnancies.

WIDER IMPLICATIONS OF THE FINDINGS

In addition to encouraging results obtained with our vitrification procedure for non-human ovarian tissue, this study also showed, for the first time, expression of AMH and GDF-9 in ovarian follicles.

STUDY FUNDING/COMPETING INTEREST(S)

This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4507.10, grant 3.4.590.08 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, Foundation Against Cancer, and Department of Mechanical Engineering at Louisiana State University (support to Ram Devireddy), and donations from Mr Pietro Ferrero, Baron Frère and Viscount Philippe de Spoelberch. None of the authors has any competing interests to declare.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2146?rss=1

STUDY QUESTION

How can leukemic cells be detected in cryopreserved ovarian tissue?

SUMMARY ANSWER

Multicolor flow cytometry (FCM) is useful to evaluate the presence of viable leukemic cells in the ovarian cortex with a high specificity and a robust sensitivity.

WHAT IS KNOWN ALREADY

Storing ovarian tissue is an option to preserve fertility before gonadotoxic radiotherapy or chemotherapy treatments. However, transplantation of cryopreserved ovarian cortex to women cured of leukemia is currently not possible due to the risk of cancer re-seeding.

STUDY DESIGN, SIZE, DURATION

We developed an automated ovarian cortex dissociation technique and we used eight-color FCM to identify leukemic cells with a series of dilutions added to ovarian single cell suspensions obtained from healthy cortex.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS

Healthy ovarian cortex originated from women between 23 and 39 years of age undergoing laparoscopic ovarian drilling for polycystic ovary syndrome. Blood or bone marrow cells were collected in acute lymphoblastic leukemia (ALL) patients at diagnosis.

MAIN RESULTS AND THE ROLE OF CHANCE

The tissue dissociation technique yield was 1.83 ± 1.49 x 10⁶ viable nucleated cells per 100 mg of ovarian cortex. No cell exhibiting a leukemic phenotype was present in the normal ovarian cortex. Added leukemic cells were detected using their leukemia-associated phenotype up to a dilution of 10^–4. When specific gene rearrangements were present, they were detected by real-time quantitative PCR at the same dilution. The ovarian cortex from two leukemia patients was then used, respectively, as positive and negative controls.

LIMITATIONS, REASONS FOR CAUTION

Making available minimal residual disease (MRD) detection techniques (multicolor FCM, PCR and xenograft), that can be used either alone or together, is essential to add a fail-safe oncological dimension to pre-autograft monitoring.

WIDER IMPLICATIONS OF THE FINDINGS

This approach can be performed on fresh ovarian tissue during cryopreservation or on frozen/thawed tissue before reimplantation and it is currently the only available technique in cases of ALL where no molecular markers are identified. This new perspective should lead to studies on ovarian tissue from leukemia patients, for whom the presence of MRD should be established before autograft.

STUDY FUNDINGS/COMPETING INTEREST(S)

The study was supported by the BioMedicine Agency, the Committee of the League against Cancer, the Besançon University Hospital, DGOS/INSERM/INCa and the regional Council of Franche-Comté. There were no conflicts of interest to declare.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2157?rss=1

STUDY QUESTION

Do the quality of life (QoL) and the risk factors for emotional problems during and after treatment of infertile women differ from their partners?

SUMMARY ANSWER

Women have lower levels of fertility-related QoL, and more and differing risk factors for emotional problems during and after treatment than their partners.

WHAT IS KNOWN ALREADY?

The psychological impact of infertility in patients negatively affects their QoL and is also related to increased discontinuation of treatment. Moreover, psychological factors might positively affect pregnancy rates. However, it is still unclear if differences in QoL and emotional status exist between infertile women and their partners. So far, research mainly focused on generic instruments to measure patients' QoL in the area of fertility care.

STUDY DESIGN, SIZE, DURATION

A cross-sectional study of infertile couples within 32 Dutch fertility clinics.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We included infertile women and their partners (both heterosexual and lesbian couples) under any treatment and at any stage of treatment in one of the 32 participating clinics. Per clinic, 25–75 patients were randomly selected depending on clinic size. In total, 1620 women and their partners were invited separately to complete the FertiQoL and SCREENIVF questionnaires to measure their level of QoL and risk factors for emotional problems during and after treatment, respectively.

MAIN RESULTS AND THE ROLE OF CHANCE

A total of 946 women (response rate 58%) and 670 partners (response rate 41%) completed the questionnaire set. As 250 women and 150 partners were already pregnant, questionnaires from 696 women and 520 partners could be analysed. Women scored significantly lower on the FertiQoL total scores [B = –6.31; 95% confidence interval (CI) = –7.63 to 4.98] and three of the FertiQoL subscales (Emotional, Mind–Body and Social) than their partners, indicating lower QoL. Scores on the SCREENIVF questionnaire were significantly higher for women (B = 0.22; 95% CI = 0.06–0.38), indicating that women are more at risk for developing emotional problems (and these factors differed from those of their partners) during and after fertility treatment than their partners.

LIMITATIONS, REASONS FOR CAUTION

Although the number of participants is high (n = 1216), the relatively low response rate, especially for partners (41%), may have influenced the results through selection bias. An analysis of non-responders could not be performed. The FertiQoL and SCREENIVF questionnaires, which have been validated only in women starting a first IVF cycle, should also be validated for studying partners. In addition, the SCREENIVF questionnaire has been validated in Dutch women only and further research in an international setting is also required.

WIDER IMPLICATIONS OF THE FINDINGS

Our study results represent the Dutch infertile population as more than one-third of all Dutch clinics participated in the study. As the FertiQoL questionnaire is an internationally validated questionnaire already, these results can be put in a more broader and international perspective.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by Merck Sharp & Dohme (MSD), The Netherlands. There are no competing interests.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2168?rss=1

STUDY QUESTION

Are clinic factors, including patients’ experiences with patient-centred care, associated with dropout in fertility care?

SUMMARY ANSWER

Clinic factors, including patients’ experiences with patient-centred care, are not related to dropout.

WHAT IS KNOWN ALREADY

In fertility care, a significant proportion of patients do not achieve pregnancy because they discontinue treatment prematurely. Many studies have tried to identify factors predicting dropout, showing incompatible results. However, these studies mainly focus on factors at the treatment and patient level, while clinic factors have received little attention.

STUDY DESIGN, SIZE, DURATION

This prospective, longitudinal study was nested within a large RCT, which aims to improve the level of patient-centredness of Dutch fertility care. Of the 1620 infertile women who were invited to participate, the baseline measurement of the study (T0) included 693 women who completed a questionnaire about their experiences with patient-centred fertility care. The follow-up of the patients was 1 year (T1).

PARTICIPANTS/MATERIALS, SETTING, METHODS

All included women suffered from infertility and were undergoing treatment in one of the 32 Dutch clinics involved in the trial. Levels of patient-centredness were determined using the Patient-Centredness Questionnaire-Infertility (PCQ-Infertility) at T0. Meanwhile, a professionals’ questionnaire was used to gather additional information on characteristics of the clinic (e.g. the number of patients per year or the presence of a fertility nurse). After 1 year, at T1 measurement, patients completed a questionnaire on their current status in fertility care, including their main reason for discontinuation if applicable.

MAIN RESULTS AND THE ROLE OF CHANCE

A total of 693 non-pregnant women completed the questionnaire set at T0 and 534 women (77.1%) provided consent for follow-up. At T1 measurement, 434 women (81.3%) completed the questionnaire and 153 of these women (35.2%) continued treatment while 76 women (17.5%) dropped out. Another 175 women (40.3%) had achieved pregnancy and 30 patients (7.9%) were advised to discontinue treatment for medical reasons. Neither levels of patient-centredness nor the additional clinic characteristics differed significantly between dropouts and compliers. However, patients who did not receive assisted reproduction treatment (ART; e.g. underwent intrauterine insemination, IUI) before they dropped out had significantly lower scores on the PCQ-Infertility subscale ‘Respect for patients’ values’ than patients who continued their treatment [odds ratio (OR) 0.57; 95% confidence interval (CI) 0.34–0.95]. Patients who received ART and, subsequently, dropped out had higher scores on the PCQ-Infertility subscale ‘Patient involvement’ than those receiving non-ART (OR 2.39; 95% CI 1.02–5.59).

LIMITATIONS, REASONS FOR CAUTION

We were not able to follow-up a significant proportion (ca. 19%) of the 1620 women who were invited for T0 measurement, which might have biased our results. We also excluded patients who were still in the diagnostic work-up stage and this might have influenced our results as it is known that patients dropout at this stage. As the PCQ-Infertility was validated in patients who were already undergoing treatment, we decided to focus on this patient group only.

WIDER IMPLICATIONS OF THE FINDINGS

The results of this study provide a better insight into those factors influencing dropout from the perspective of factors in the clinic itself. Although most clinic factors were not related to dropout, clinic factors might be of use when predicting dropout for specific patient groups, such as patients receiving ART and non-ART. Future research should involve an exploration of more specific predictors of dropout at the patient, treatment and clinic levels.

STUDY FUNDING/COMPETING INTERESTS

This work was supported by Merck Serono, the Netherlands. No competing interests declared.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/8/2177?rss=1

Human Reproduction Ayelin et al
Students created videos using play-dough and cut outs of what they learned about Human Reproduction. This is one example from my class.

By: Dawnette Brenner

Go here to see the original:
Human Reproduction Ayelin et al - Video

STUDY QUESTION

Which strategy is least expensive to prevent the birth of a handicapped child in couples with recurrent miscarriage (RM); parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents, or amniocentesis in all ongoing pregnancies without the knowledge of parental carrier status?

SUMMARY ANSWER

For virtually all couples with RM amniocentesis in all ongoing pregnancies without the knowledge of parental carrier status is less expensive in preventing the birth of a handicapped child than parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents.

WHAT IS KNOWN ALREADY

One of the causes of RM is a balanced chromosome abnormality in one of the partners. If one of the partners is carrier of a balanced structural chromosomal abnormality, the risk of offspring with an unbalanced structural chromosome abnormality is increased. Like all couples, couples with RM also have an age-dependent risk for fetal aneuploidy, of which trisomy 21 is most common.

STUDY DESIGN, SIZE, DURATION

Model-based economic analysis to compare costs and effects of two strategies in couples with RM to prevent the birth of a handicapped child in case of ongoing pregnancy.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Comparison of two strategies in women with RM: strategy (I) parental chromosome analysis followed by amniocentesis in pregnancy in case of carrier status of one of the parents and strategy (II) amniocentesis in all ongoing pregnancies without the knowledge of carrier status. No testing was the reference strategy. Data on probabilities and costs were derived from the literature. Incremental costs and effects were calculated [incremental cost-effectiveness ratio (ICER)]. Effectiveness was expressed as the number of prevented births of handicapped child equivalents compared with no testing. In these calculations, the birth of a handicapped child was valued 10 times worse than the loss of a viable pregnancy due to amniocentesis.

MAIN RESULTS AND THE ROLE OF CHANCE

Depending on the risk for carrier status, the ICER for Strategy I (parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents) varied between 226 000 and 6 556 000 per prevented handicapped child equivalent. For Strategy II (amniocentesis in all ongoing pregnancies without the knowledge of carrier status), the ICER varied between 2000 and 233 000 per prevented handicapped child equivalent. Strategy I was less expensive than Strategy II only for a small subgroup of couples with maternal age <23 years, three or more previous miscarriages and a family history of RM.

LIMITATIONS, REASONS FOR CAUTION

Our analysis is not a plea for amniocentesis in all women with RM. Individual risk assessment with serum markers and nuchal translucency is probably more effective at lower cost.

WIDER IMPLICATIONS OF THE FINDINGS

This analysis can be used by clinicians to explain the chances of adverse pregnancy outcome in couples with RM, as well as by policy makers in health-care economics. Future guidelines on RM might be more restrictive from the perspective of the limited health-care resources that we have available.

STUDY FUNDING/COMPETING INTEREST(S)

Supported by ZonMW. ZonMW had no role in designing the study, data collection, analysis and interpretation of data or writing of the report. Competing interests: none.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/7/1737?rss=1

STUDY QUESTION

Is it feasible to screen women with idiopathic recurrent miscarriage (RM) for high uterine natural killer (uNK) cell density and then randomize them to prednisolone or placebo when pregnant?

SUMMARY ANSWER

It was feasible to recruit women with idiopathic RM into a ‘screen and treat’ trial despite their desire for active medication.

WHAT IS KNOWN ALREADY

Clinical trials of immunotherapy in women with idiopathic RM have failed to substantiate efficacy in preventing miscarriage. Preimplantation  uNK cell density is higher in women with RM and can be reduced with prednisolone.

STUDY DESIGN, SIZE, DURATION

In a pilot RCT, 160 eligible women were screened with an endometrial biopsy and those with high uNK cell density were invited to return when pregnant for randomization to prednisolone (20 mg for 6 weeks, 10 mg for 1 week, 5 mg for 1 week) or identical placebo tablets. Randomization was by random number generation and patients, clinicians and outcome assessors were blinded to allocation. The study size and duration was determined by funding, which was for a feasibility trial, for 2 years, sufficient to screen 150 women and randomize 40 women. The outcome measures were recruitment rate, women's perspectives, compliance, live birth and miscarriage rates and pregnancy complications.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The trial was advertised nationally in the UK. Women who attended research clinics run by one consultant (SQ) with three or more consecutive idiopathic miscarriages were included. Women's perspectives of the trial were sought through a questionnaire. The endometrium was sampled 5–9 days after the LH surge, stained using immunohistochemistry for CD56 and the sub-epithelial region analysed with image analysis. Women with a high uNK cell density (>5%) were invited to contact the clinic at 4–6 weeks gestation for randomization. Compliance with medication was assessed using a daily log, and side effects recorded by the women in a diary and on a structured proforma completed in the clinic at the end of the first trimester. All women had ultrasound scans every 2 weeks until 14 weeks’ gestation and growth scans at 28 and 34 weeks’ gestation in addition to routine antenatal care and a follow-up in person or by telephone 6 weeks after delivery.

MAIN RESULTS AND THE ROLE OF CHANCE

Despite the fact that 85% of women said they would prefer the active treatment, the trial recruitment occurred at the planned rate. Eligible women (n = 160) attended the research clinics and had the uNK test, 72 were screen positive and 40 returned when pregnant for randomization. Compliance with medication was reported to be 100%. The active treatment was associated with side effects of insomnia and flushing. The live birth rate was 12/20 (60%) with prednisolone and 8/20 (40%) with placebo (Risk Ratio 1.5, 95% confidence interval (CI) 0.79–2.86, absolute difference 20% CI-10%, +50%), and hence, this was not significant. There were no pregnancy complications or serious adverse fetal outcomes.

LIMITATIONS, REASONS FOR CAUTION

This was a feasibility trial so of insufficient size to assess efficacy or safety. There was inconsistency in the start date of the trial medication and this may have affected the outcome in the active treatment group.

WIDER IMPLICATIONS OF THE FINDINGS

It was feasible to recruit women with idiopathic RM into a ‘screen and treat’ trial despite their desire for active medication. Our data also suggest that in future trials the primary outcome measure is live birth rate after 24 weeks gestation.

STUDY FUNDING/COMPETING INTEREST(S)

Moulton charitable trust funded this study. There are no competing interests.

TRIAL REGISTRATION NUMBER

Current Controlled Trials No: ISRCTN28090716.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/7/1743?rss=1

Here are some quotes for Fr. John J.Pasquini’s book Medicine of Immortality. This book can be ordered from Shepherds of Christ Ministries. “ Fr. John Pasquini’s ...

See more here:
Medicine of Immortality - Treasures From The Hearts of ...

STUDY QUESTION

How do human embryonic growth trajectories evolve in the first trimester, and is first-trimester embryonic growth associated with fetal growth and birthweight (BW)?

SUMMARY ANSWER

Human embryonic growth rates increase between 9 and 10 weeks of gestation and are associated with mid-pregnancy fetal growth and BW.

WHAT IS KNOWN ALREADY

Fetal growth is associated with health and disease risks in later life. Until recently, prenatal care and research have been focused predominantly on fetal growth in the second and third trimesters of pregnancy. Longitudinal first-trimester data remain scarce.

STUDY DESIGN, SIZE, DURATION

We recruited 201 pregnancies before 8 weeks of gestation in a prospective periconception cohort study conducted in a tertiary center.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We performed weekly 3D ultrasound scans from enrollment up to 13 weeks of gestation. To create embryonic growth trajectories, serial crown–rump length (CRL) measurements were performed using the V-Scope software in the BARCO I-Space. Mid-pregnancy fetal growth parameters and BW were obtained from medical records. Z-scores were calculated for CRL, mid-pregnancy estimated fetal weight (EFW) and BW. Associations between embryonic and fetal growth parameters were investigated using Pearson's correlation coefficients.

MAIN RESULTS AND THE ROLE OF CHANCE

During the early first trimester (up to 9 weeks of gestation), we observed a constant absolute mean embryonic CRL growth rate of 0.99 mm/day (SD 0.10), while the relative growth rate decreased. Between 9 and 10 weeks of gestation, the absolute growth rate increased, and during late first trimester (from 10 weeks of gestation onward), we observed a constant mean relative growth rate of 4.1% (SD 0.006) per day. Overall, early and late first-trimester median CRL Z-scores were strongly correlated with mid-pregnancy EFW (r_{overall/early/late} = 0.57/0.57/0.54, P < 0.001) but only overall and late CRL Z-scores were correlated with BW (r_overall = 0.15, P = 0.04; r_early = 0.10, P = 0.17; r_late = 0.17, P = 0.02).

LIMITATIONS, REASONS FOR CAUTION

This study was conducted in a tertiary hospital. Therefore, future studies in other populations are warranted to confirm our results.

WIDER IMPLICATIONS OF THE FINDINGS

This study shows differences between early and late first-trimester embryonic growth coinciding with changes in intrauterine nourishment. The established associations between first-trimester embryonic growth and fetal size in mid-pregnancy and at birth emphasize that more research is warranted to establish the importance of these results for preconceptional and early pregnancy care.

STUDY FUNDING/COMPETING INTEREST(S)

This work was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/7/1753?rss=1

STUDY QUESTION

What factors does multivariate logistic regression show to be significantly associated with the likelihood of clinical pregnancy in vitrified–warmed embryo transfer (VET) cycles?

SUMMARY ANSWER

Assisted hatching (AH) and if the reason to freeze embryos was to avoid the risk of ovarian hyperstimulation syndrome (OHSS) were significantly positively associated with a greater likelihood of clinical pregnancy.

WHAT IS KNOWN ALREADY

Single factor analysis has shown AH, number of embryos transferred and the reason of freezing for OHSS to be positively and damaged blastomere to be negatively significantly associated with the chance of clinical pregnancy after VET. It remains unclear what factors would be significant after multivariate analysis.

STUDY DESIGN, SIZE, DURATION

The study was a retrospective analysis of 2313 VET cycles from 1481 patients performed between January 2008 and April 2012. A multivariate logistic regression analysis was performed to identify the factors to affect clinical pregnancy outcome of VET.

PARTICIPANTS/MATERIALS, SETTING, METHODS

There were 22 candidate variables selected based on clinical experiences and the literature. With the thresholds of α_entry = α_removal= 0.05 for both variable entry and variable removal, eight variables were chosen to contribute the multivariable model by the bootstrap stepwise variable selection algorithm (n = 1000). Eight variables were age at controlled ovarian hyperstimulation (COH), reason for freezing, AH, endometrial thickness, damaged blastomere, number of embryos transferred, number of good-quality embryos, and blood presence on transfer catheter. A descriptive comparison of the relative importance was accomplished by the proportion of explained variation (PEV).

MAIN RESULTS AND THE ROLE OF CHANCE

Among the reasons for freezing, the OHSS group showed a higher OR than the surplus embryo group when compared with other reasons for VET groups (OHSS versus Other, OR: 2.145; CI: 1.4–3.286; Surplus embryos versus Other, OR: 1.152; CI: 0.761–1.743) and high PEV (marginal 2.77%, P = 0.2911; partial 1.68%; CI of area under receptor operator characteristic curve (ROC): 0.5576–0.6000). AH also showed a high OR (OR: 2.105, CI: 1.554–2.85) and high PEV (marginal 1.97%; partial 1.02%; CI of area under ROC: 0.5344–0.5647). The number of good-quality embryos showed the highest marginal PEV and partial PEV (marginal 3.91%, partial 2.28%; CI of area under ROC: 0.5886–0.6343).

LIMITATIONS, REASONS FOR CAUTION

This was a retrospective multivariate analysis of the data obtained in 5 years from a single IVF center. Repeated cycles in the same woman were treated as independent observations, which could introduce bias. Results are based on clinical pregnancy and not live births. Prospective analysis of a larger data set from a multicenter study based on live births is necessary to confirm the findings.

WIDER IMPLICATIONS OF THE FINDINGS

Paying attention to the quality of embryos, the number of good embryos, AH and the reasons for freezing that are associated with clinical pregnancy after VET will assist the improvement of success rates.

STUDY FUNDING/COMPETING INTEREST(S)

This study was financially supported by the Scientific and Technological Research Projects of Shaanxi Province (project number: 2011k15-02-01). All the authors have no conflict of interest to declare.

TRIAL REGISTRATION NUMBER

N/A.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/7/1768?rss=1

STUDY QUESTION

Can time-lapse analysis of cell division timings [morphokinetics (MK)] in mouse embryos detect toxins at concentrations that do not affect blastocyst formation?

SUMMARY ANSWER

An MK algorithm enhances assay sensitivity while providing results 24–48 h sooner than the traditional mouse embryo assay (MEA).

WHAT IS KNOWN ALREADY

Current quality control testing methodology is sensitive but further improvements are needed to assure optimal culture conditions. MKs of embryo development may detect small variations in culture conditions.

STUDY DESIGN

Cross sectional—control versus treatment. Mouse embryo development kinetics of 466 embryos were analyzed according to exposure to various concentrations of toxins and toxic mineral oil.

MATERIALS, SETTING, METHODS

Cryopreserved 1-cell embryos from F1 hybrid mice were cultured with cumene hydroperoxide (CH) (0, 2, 4, 6 and 8 µM) and Triton X-100 (TX-100; 0, 0.0008, 0.0012, 0.0016 and 0.002%). Using the Embryoscope, time-lapse images were obtained every 20 min for 120 h in seven focal planes. End-points were timing and pattern of cell division and embryo development. The blastocyst rate (BR) was defined as the percentage of embryos that developed to the expanded blastocyst stage within 96 h.

MAIN RESULTS AND THE ROLE OF CHANCE

BR was not affected for embryos cultured in the three lowest concentrations of CH and the four lowest concentrations of TX-100. In contrast, a unique MK model detected all concentrations tested (P < 0.05). The MK model identified toxicity in two lots of toxic mineral oil that did not affect BR (P < 0.05).

LIMITATIONS, REASONS FOR CAUTION

A limited number of toxins were used so that the results may not apply to all potential embryo toxins. A larger sample size may also demonstrate other statistically significant developmental kinetic parameters.

WIDER IMPLICATIONS OF THE FINDINGS

MKs in mouse embryos are a sensitive and efficient method for quality control testing of in vitro culture conditions. BR, the end-point of traditional quality control assays, did not detect sublethal concentrations of toxins in the culture milieu in our study. This study demonstrates that temporal variation at key developmental stages reflects the quality of the culture environment. An MEA that incorporates MK will provide enhanced sensitivity and faster turn-around times.

STUDY FUNDING/COMPETING INTEREST(S)

The study was supported by Mayo Clinic Department of Obstetrics and Gynecology Small Grant Program. The authors have no competing interests to declare.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/7/1776?rss=1