Jacqueline Pui Wah Chung

Dynamic changes of DNA epigenetic marks in mouse oocytes during natural and accelerated aging.

Aging is a complex time-dependent biological process that takes place in every cell and organ, eventually leading to degenerative changes that affect normal biological functions. In the past decades, the number of older parents has increased significantly. While it is widely recognized that oocyte aging poses higher birth and reproductive risk, the exact molecular mechanisms remain largely elusive. DNA methylation of 5-cytosine (5mC) and histone modifications are among the key epigenetic mechanisms involved in critical developmental processes and have been linked to aging. However, the impact of oocyte aging on DNA demethylation pathways has not been examined. The recent discovery of Ten-Eleven-Translocation (TET) family proteins, thymine DNA glycosylase (TDG) and the demethylation intermediates 5hmC, 5fC and 5caC has provided novel clues to delineate the molecular mechanisms in DNA demethylation. In this study, we examined the cellular level of modified cytosines (5mC, 5hmC, 5fC and 5caC) and Tet/Tdg expression in oocytes obtained from natural and accelerated oocyte aging conditions. Here we show all the DNA demethylation marks are dynamically regulated in both aging conditions, which are associated with Tet3 over-expression and Tdg repression. Such an aberrant expression pattern was more profound in accelerated aging condition. The results suggest that DNA demethylation may be actively involved in oocyte aging and have implications for development of potential drug targets to rejuvenate aging oocytes. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.

Assessment of the embryo flash position and migration with 3D ultrasound within 60 min of embryo transfer

STUDY QUESTION Does the air bubble (embryo flash) position and migration as visualized with 3D ultrasound (US) within 60 min of embryo transfer correlate with clinical outcome following fresh ART transfer cycles? SUMMARY ANSWER The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, are associated with clinical pregnancy. WHAT IS KNOWN ALREADY Studies assessing the relation between the pregnancy rate and the position of the catheter tip and/or the position of the air bubbles following embryo transfer show conflicting results to date. STUDY DESIGN, SIZE AND DURATION This was a prospective cohort study including 277 infertile women undergoing ART between July 2011 and August 2013. PARTICIPANTS/MATERIALS, SETTING AND METHODS Good prognosis patients undergoing fresh ART cycles within a single tertiary University unit were assessed by 3D US at 1, 5 and 60 min after embryo transfer. The distance of the embryo flash from the fundus was measured at these time points, along with the direction of the embryo flash movement within 60 min of transfer. MAIN RESULTS AND THE ROLE OF CHANCE Within 60 min of embryo transfer, 76.4% (198/259) of the embryo flashes migrated towards the fundus, 12.4% (32/259) migrated towards the cervix and 11.2% (29/259) remained static. There was no significant association between the embryo position or movement and the pregnancy rate at 1 and 5 min. At 60 min, however, the pregnancy and implantation rates among subjects with embryo flashes located <15 mm from the fundus was significantly higher than those with embryo flashes located >15 mm from the fundus (46.5 and 32.8% versus 25.8 and 18.2%, respectively; P < 0.05). The pregnancy and implantation rates when the embryo flash was seen moving towards the cervix (25.0 and 15.0%) was significantly lower (P < 0.05 and P < 0.01, respectively) compared with those remaining static (55.2 and 37.7%) or moving towards the fundus (45.5 and 32.8%). LIMITATIONS AND REASONS FOR CAUTION Although the air bubbles seen at the time of embryo transfer are thought to represent the position of the embryo, they are in fact a surrogate marker of the embryo itself, as this cannot be directly visualized by US. WIDER IMPLICATIONS OF THE FINDINGS Following embryo transfer the majority, but not all, embryo flashes undergo significant migration towards the fundus. The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, is associated with clinical outcome. These findings may challenge the traditional notion that the exact position of the embryo flash immediately following embryo transfer is related to clinical outcome. STUDY FUNDING/COMPETING INTERESTS The authors have no relevant funding or conflicts of interest to disclose.

A randomized crossover study of medroxyprogesterone acetate and Diane-35 in adolescent girls with polycystic ovarian syndrome.

OBJECTIVE To investigate the effects of 4-month treatment of medroxyprogesterone acetate (MPA) and Diane-35 on the clinical and biochemical features of hyperandrogenism and quality of life of adolescent girls with polycystic ovarian syndrome (PCOS). DESIGN A prospective, randomized, cross-over study. SETTING An accredited pediatric and adolescent gynecology clinic of a university-affiliated tertiary hospital. PARTICIPANTS 76 adolescents girls aged 14 to 19 years old with PCOS were recruited from July 2007 to July 2010. INTERVENTIONS Girls were randomized into 2 groups. Group 1 received oral MPA for 4 months, followed by a washout period of 4 months, and then Diane-35 for another 4 months. Group 2 received the same combination but in the reverse order. MAIN OUTCOME MEASURES Clinical and biochemical features of hyperandrogenism and quality of life were assessed. RESULTS There was no significant difference between the 2 groups at baseline. No significant difference was found in the clinical and biochemical parameters of hyperandrogenism before and after treatment with MPA. Significant reduction of the acne score, LH/FSH ratio, and testosterone level was seen after taking Diane-35. Hirsutism was also improved but it did not reach statistical significant. When comparing post-MPA and post-Diane-35, the post-Diane-35 group had significantly improved acne score and LH/FSH ratio. No significant difference was found on quality of life between both groups after treatment. CONCLUSION Diane-35 may be a more suitable treatment option in adolescent girls diagnosed with PCOS when compared to MPA.

Long‐term reproductive outcome after hysteroscopic proximal tubal cannulation – an outcome analysis

The optimal therapeutic method for proximal tubal obstruction (PTO) has yet to be defined. In addition, the reported successful recanalisation rate and reproductive outcome from hysteroscopic proximal tubal cannulation have been inconsistent.

The effect of endometrial scratch on natural-cycle cryopreserved embryo transfer outcomes: a randomized controlled study

The benefit of endometrial scratch (ES) prior to embryo transfer is controversial. Systemic analysis has confirmed its potential benefit, especially in women with repeated IVF failures, yet most studies have focused on fresh embryo transfer, and its effect on vitrified-warmed embryo transfer (FET) cycles is yet to be explored. We hereby present our prospective, double-blind, randomized controlled study on the evaluation of the implantation and pregnancy rate after ES prior to natural-cycle FET. A total of 299 patients underwent natural-cycle FET and were randomized to receive ES (n = 115) or endocervical manipulation as control (n = 114) prior to FET cycle, and a total of 196 patients had embryo transfer (93 patients in each group). Our study showed no significant difference in the implantation and pregnancy rate, as well as the clinical and ongoing pregnancy or live birth rates between the two groups. It appears that ES does not have any beneficial effect on an unselected group of women undergoing FET in natural cycles. Further studies on its effect in women with recurrent implantation failure after IVF are warranted.

The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical outcome

In this prospective cohort study of 286 women undergoing fresh embryo transfer after IVF, uterine contraction frequency and direction were measured before (-5 min), 5 min after (+5 min) and 60 min after (+60 min) embryo transfer. Mean ± SD uterine contraction frequency at -5 min was 1.8 ± 1.1 contractions per min, increasing significantly (P < 0.05) to 2.0 ± 1.1 at +5 min, and returning back to baseline 1.8 ± 1.1 at +60 min. At -5 min, the proportion of women the with retrograde, antegrade, indeterminate direction and absent contractions were 33%, 44%, 17% and 6%; at +5 min, 40%, 42%, 13% and 5%, and at +60 min, 42%, 38%, 14% and 6%. No significant change was observed in the proportion of direction at these three time points. Logistic regression analysis showed live birth rate was significantly reduced in older women (P = 0.035) and in those with higher uterine contraction frequency at +5 min (P = 0.006). Frequency of uterine contraction immediately after embryo transfer (+5 min) seemed to be a significant predictor of IVF outcome and may help to identify women who could benefit from the use of muscle relaxant therapy to improve outcome.

Efficacy, feasibility and patient acceptability of ultrasound‐guided manual vacuum aspiration for treating early pregnancy loss

Ultrasound‐guided manual vacuum aspiration (USG‐MVA) is an effective but underutilised alternative to medical or surgical evacuation of the uterus following first trimester miscarriage.

Uses of FloSeal© in obstetric hemorrhage: Case series and literature review

OBJECTIVE FloSeal© has been shown to be an alternative and effective method of hemostasis. The current study examines the various uses of FloSeal© in obstetric hemorrhage and gives an overview of the literature. CASE REPORTS In this retrospective case review, a total of 11 cases with obstetric hemorrhage were reviewed throughout a period of one year. All but one case was successful in using FloSeal© in arresting the bleeding with hysterectomy avoided. FloSeal© can be considered when bleeding occurs locally at the placental bed, bladder base, adhesiolysis site, vaginal tears or at suture holes. CONCLUSION FloSeal© was a quick and effective alternative for hemostasis and should be considered when conventional hemostatic techniques fails or is impractical.

Increased expression of angiogenic cytokines in CD56+ uterine natural killer cells from women with recurrent miscarriage

HighlightsCD56+ uNK cells produce angiogenic factors around the time of implantation.An increased expression of angiogenic factors in uNK cells was observed in RM.The altered expression may associate with underlying endometrial pathology in RM. Objective: To compare the expression pattern of angiogenic cytokines in CD56+ uNK cells from peri‐implantation endometrium in women with a history of recurrent miscarriage and fertile controls. Methods: 28 women were recruited, from which 18 women were diagnosed as recurrent miscarriage and 10 women were of proven fertility. Endometrial biopsy samples were obtained precisely 7 days after luteinization hormone surge in a natural cycle. The angiogenic profile of isolated CD56+ uNK cells was determined by RayBio human angiogenesis antibody array G Series 1000. Differentially expressed angiogenic cytokines between groups were validated by ELISA kits. Results: CD56+ uNK cells freshly isolated from peri‐implantation endometrium were determined to be >90% pure. Angiogenic cytokine array demonstrated that CD56+ uNK cells are one of the angiogenic factors producers in endometrium around the time of embryo implantation. A differential angiogenic cytokine expression profile was found between two groups, with significantly higher expressions of angiogenin, VEGF‐A and bFGF in CD56+ uNK cells from women with recurrent miscarriage, compared with fertile controls. Conclusions: Differential angiogenic cytokine profile of isolated CD56+ uNK cells suggested the role of uNK cells in the altered endometrial vascularity at the time of implantation, which may account for the endometrial contribution to recurrent miscarriage.

The Investigation and Management of Adenomyosis in Women Who Wish to Improve or Preserve Fertility

The management of adenomyosis remains a great challenge to practicing gynaecologists. Until recently, hysterectomy has been the only definitive treatment in women who have completed child bearing. A number of nonsurgical and minimally invasive, fertility-sparing surgical treatment options have recently been developed. This review focuses on three aspects of management, namely, (1) newly introduced nonsurgical treatments; (2) management strategies of reproductive failures associated with adenomyosis; and (3) surgical approaches to the management of cystic adenomyoma.