Sonographer-guided frozen embryo transfer vs ultrasound-assisted frozen embryo transfer - A randomised controlled study.

BACKGROUND: The use of ultrasound to guide placement of the embryo during in vitro fertilisation (IVF) is important, but there are times where a good image cannot be obtained. Having a trained sonographer perform the ultrasound may therefore improve the success of embryo transfer. AIM: To determine whether the routine use of a sonographer to guide embryo transfer is superior to standard care. MATERIALS AND METHODS: Randomised, controlled, prospective clinical study in a private infertility clinic. There were 113 women aged <38 years undergoing frozen embryo transfer (donor egg/embryo excluded) who were randomised to sonographer-guided embryo transfer or standard care (the doctor performs an ultrasound prior to embryo transfer and the patient holds the ultrasound probe). The primary outcome was visualisation of the air bubble, and secondary outcomes were distance of the air bubble from the fundal endometrium, pregnancy rate (gestational sac on ultrasound at seven weeks) and live birth rate. RESULTS: The bubble was visualised in 100% of embryo transfers with a sonographer compared to 83% in the ultrasound-assisted group, and this was statistically significant (P < 0.01). No statistically significant differences were found in terms of distance from the fundal endometrium or in pregnancy rate and live birth rate. CONCLUSION: Sonographer-guided embryo transfer leads to statistically higher rates of visualisation of the air bubble compared to ultrasound-assisted transfer.

The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review.

STUDY QUESTION: Can controlled ovarian hyperstimulation (COH) for fertility preservation be effectively conducted in women with breast cancer without worsening their prognosis? SUMMARY ANSWER: COH with co-administration of letrozole suppresses oestradiol levels without significantly impacting oocyte yield or decreasing disease-free survival rates. WHAT IS KNOWN ALREADY: Oestradiol has the capacity to stimulate the proliferation of breast cancer cells. COH can cause oestradiol levels to rise by an order of magnitude above physiological levels. Concern exists regarding the effect of supra-physiological oestradiol levels in women with a recent diagnosis of breast cancer. STUDY DESIGN, SIZE, DURATION: A systematic review of the literature was performed using MEDLINE (PubMed database), EMBASE and the Cochrane Library. The search was restricted to articles written in English. No restrictions regarding the date of publication were applied. Safety was assessed in terms of relapse rates and cancer-related mortality rates. Peak oestradiol concentrations were recorded for different stimulation protocols. Efficacy was measured in terms of the total number of oocytes collected and proportion of mature oocytes. The primary outcome was mortality/recurrence in premenopausal women with Stage I-IIIB breast cancer who underwent COH in the immediate post-operative period, prior to chemotherapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: This is a systematic review of randomized control trials (RCTs), case control and cohort studies reporting on the primary outcome of mortality/recurrence after COH in women with early breast cancer, or secondary outcomes of oocyte yield and peak oestrogen concentration. Owing to the small number of RCTs available, other study types were included. The last electronic search was run in April 2016. Two prospective non-randomized studies reported relapse and breast cancer-related mortality rates in 397 women with breast cancer, of whom 149 underwent COH. Twelve studies reported the peak oestradiol concentrations of 882 women undergoing COH with letrozole co-administration. Four studies compared the oocyte yield of 248 women who underwent COH plus letrozole with 254 women who underwent standard COH. Two studies compared peak oestradiol concentrations and oocyte yield in 61 women who underwent COH with tamoxifen co-administration and 49 women who underwent COH without tamoxifen. One study compared letrozole and tamoxifen co-administration, and another study compared the co-administration of letrozole and anastrozole. MAIN RESULTS AND THE ROLE OF CHANCE: The search identified 1002 records of which 15 were included in the final analysis. There was no evidence of a decline in relapse-free survival rates in the two studies of women with breast cancer who received COH with letrozole co-administration compared with women who did not undergo fertility preservation procedures. The largest of these studies reported recurrences in 6/120 (5.0%) women who received COH plus letrozole compared with 12/217 (5.5%) women who did not undergo COH (mean follow-up 5.0 versus 6.9 years; hazard ratio for recurrence 0.77, 95%CI 0.28-2.13). Conclusions regarding women with breast cancer who received tamoxifen during COH could not be made due to insufficient data. Peak oestradiol concentrations (338-829 pg/ml) were suppressed by letrozole when commenced on Days 2-3, with no decrease in oocyte yield. Tamoxifen does not suppress oestradiol concentrations, but may convey protection via its inhibitory action on the oestrogen receptor. LIMITATIONS, REASONS FOR CAUTION: Any statements regarding the safety of COH in women with breast cancer are based on a limited number of observational studies. High quality evidence is unlikely to become available for ethical and practical reasons. Whilst available data do not indicate a decline in disease-free survival, a small effect cannot be excluded. Breast cancers are heterogeneous in their genetic profile and receptor status, making the results of studies difficult to generalize to individual cases. The implication of alterations in other hormone levels such as androgens, progestins or vascular endothelial growth factor secondary to COH in women with breast cancer has not been quantified. WIDER IMPLICATIONS OF THE FINDINGS: The co-administration of 5 mg of letrozole daily commencing on Day 2 and continuing throughout COH is recommended as it reduces peak oestradiol concentrations without significantly decreasing oocyte yield. The use of a GnRH agonist trigger is beneficial as oestradiol concentrations rapidly decrease post-administration and rates of ovarian hyperstimulation are lower than with an hCG trigger, without a corresponding reduction in clinical pregnancy or live birth rates in cryopreservation cycles. The protective effect of tamoxifen has not been evaluated although theoretically may be of benefit due to its action on the oestrogen receptor. STUDY FUNDING/COMPETING INTEREST(S): None. REGISTRATION NUMBER: None.

Live birth resulting from a conjoined oocyte confirmed as euploid using array CGH: a case report.

The significance of conjoined oocytes in the clinical IVF laboratory setting has been of question due to the extremely limited data available. The most reliable criterion for true binovularity is the inclusion of two oocytes within a common zona pellucida or their fusion in the zonal region. This is a relatively rare event and owing to the limited number of embryo transfers performed and information on their outcomes, it is highly probable that these oocytes would be discarded without attempts at fertilization and subsequent embryo culture. To our knowledge, this is the first reported pregnancy resulting from a conjoined oocyte. Our experience involved a blastocyst transfer of a genetically screened embryo, performed after removal of the germinal vesicle from the conjoined oocyte/embryo on day 3. A clinical pregnancy with a gestational sac and fetal heartbeat was achieved and a healthy baby girl was delivered via Caesarean section at 37 weeks' gestation.

GnRH agonist trigger and a freeze-all strategy to prevent ovarian hyperstimulation syndrome: a retrospective study of OHSS risk and pregnancy rates.

AIMS: To analyse the data from all controlled ovarian hyperstimulation antagonist cycles that used an agonist trigger and a freeze-all strategy to quantify the risk of ovarian hyperstimulation syndrome (OHSS) and subsequent pregnancy rates. MATERIALS AND METHODS: A retrospective study of all women attending fertility clinics at IVF Australia, Sydney, undergoing controlled ovarian hyperstimulation (COH) using an antagonist protocol that had a subsequent gonadotropin-releasing hormone (GnRH) agonist trigger and freezing of all oocytes or embryos. The primary outcome measure was to determine the rate of OHSS. The secondary outcome measure was the clinical pregnancy rate. RESULTS: We collected data for 123 women. 25.2% were undergoing oocyte freezing and 74.8% underwent embryo freezing. There were no cases of OHSS, either early or late onset. The pregnancy rate was 31.7% after the first frozen cycle transfer with a cumulative pregnancy rate of 50% after two frozen embryo transfers. CONCLUSION: Our results support the hypothesis that a GnRH agonist trigger and a freeze-all approach prevents OHSS with a good pregnancy rate.

Ovarian stimulation protocols for onco-fertility patients.

PURPOSE: To review options for ovarian stimulation before oocyte collection for fertility preservation for women with cancer or related diseases who require potentially sterilizing chemo- or radiotherapy. METHODS: Narrative review of current practice. RESULTS: Vitrification of oocytes and embryos has improved chances of pregnancy for this group of patients in recent years, increasing the uptake of fertility preservation before cancer treatment substantially. Strategies for ovarian stimulation for such patients should optimize oocyte yield whilst avoiding risk of ovarian hyperstimulation. CONCLUSIONS: Best practice in ovarian stimulation can deliver good numbers of oocytes or embryos for cryopreservation with minimal risk of ovarian hyperstimulation for women under 36 years of age. Results are less encouraging for older patients.

Endometriosis and infertility - a consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence).

Endometriosis is common in women with infertility but its management is controversial and varied. This article summarises the consensus developed by a group of Australasian subspecialists in reproductive endocrinology and infertility (the Australasian CREI Consensus Expert Panel on Trial evidence group) on the evidence concerning the management of endometriosis in infertility. Endometriosis impairs fertility by causing a local inflammatory state, inducing progesterone resistance, impairing oocyte release and reducing sperm and embryo transport. Medical treatments have a limited role, whereas surgical and assisted reproductive treatments improve pregnancy rates. The role of surgery for deep infiltrative endometriosis and repeat surgery requires further evaluation and there is insufficient evidence for the use of anti-adhesives to improve fertility. Intrauterine insemination (IUI) and in vitro fertilisation (IVF) improve pregnancy rates but women with endometriosis have lower pregnancy rates than those with other causes of infertility. The decision about whether to operate or pursue assisted reproduction will depend on a variety of factors such as the patient's symptoms, the presence of complex masses on ultrasound, ovarian reserve and ovarian access for IVF, risk of surgery and cost. Some women with infertility and endometriosis may benefit from a combination of assisted reproduction and surgery.

Basic surgical skills training: does it work?

BACKGROUND AND AIM: We assessed the RANZCOG Basic Surgical Skills Workshop (BSSW) with regards to trainees' basic knowledge and skill using a laparoscopic pelvi-trainer. METHODS: First-year trainees answered a multiple choice questionnaire (MCQ) and performed timed simulated laparoscopic exercises with a pelvi-trainer before completing a 2-day workshop. Assessment was repeated following the workshop, at 6 months and 5 years. RESULTS: MCQ results improved immediately after the workshop (baseline 16/34 vs post-course 23/34; P = 0.0001) declined at 6 months (post-course 24/34 vs 6 months 20/34; P = 0.009) with no change at 5 years (20/34 at 5 years). The time to complete both the simple and the complex laparoscopic exercises improved significantly following the workshop (simple: baseline 30 s, post-course 23 s; P = 0.008, complex: baseline 219 s, post-course 145 s; P = 0.0001) and was maintained at 6 months (simple: post-course 22 s, 6 months 23 s; P = 0.644, complex: post-course 124 s, 6 months 125 s; P = 0.958), but the time to complete the simple exercise was no better at 5 years and the time to complete the complex exercise was increased at 5 years (6 months 115 s, 5 years 172 s, P = 0.023). CONCLUSIONS: First-year trainees' basic knowledge of electrosurgery, hysteroscopy and laparoscopy and the time to perform skills on a laparoscopic pelvi-trainer improved after a BSSW but there was no further improvement at 5 years.

GnRH agonist triggers and their use in assisted reproductive technology: the past, the present and the future.

Gonadotropin releasing hormone agonist triggers are very effective in eliminating early-onset ovarian hyperstimulation syndrome (OHSS). However, in most studies they result in inferior pregnancy rates compared to hCG triggers in fresh autologous transfers. This is not due to an effect on embryo quality but rather due to inadequate corpus luteum formation and a defective luteal phase causing poor implantation. Intensive and adjusted steroid support or low-dose hCG may correct this. Late-onset OHSS is eliminated by using a freeze-all strategy. Pregnancy rates after transfer of thawed vitrified embryos are consistently high. A strategy combining a gonadotropin releasing hormone agonist trigger with vitrification of all embryos has been proposed as a means of achieving a truly OHSS-free clinic.

Twice-frozen embryos are no detriment to pregnancy success: a retrospective comparative study.

OBJECTIVE: To compare the pregnancy rates (PR) and live birth rates in once- versus twice-frozen ET treatment cycles in the same cohort of women. DESIGN: A retrospective study. SETTING: Fertility clinics, IVF Australia, New South Wales. PATIENT(S): The study population was all women who underwent thawing of twice-frozen embryos between January 2003 and May 2009. INTERVENTION(S): Twice-frozen, twice-thawed embryos. MAIN OUTCOME MEASURE(S): Pregnancy and live birth rate. RESULT(S): There were 44 women who had 52 twice-frozen ET treatment cycles. The mean age of the women was 32 ± 4.4 years and the mean number of embryos transferred was 1.1 in both the once-frozen and twice-frozen ET treatment cycles. Twice-frozen embryos had a lower post-thaw survival rate compared with the once-frozen embryos. There was no significant difference in the clinical PR or live birth rate per ET between twice-frozen and once-frozen ETs. CONCLUSION(S): Twice-frozen-thawed embryos have a lower post- thaw survival rate but equivalent pregnancy and live birth rates to once-frozen embryos. Further studies are necessary to confirm our findings and to assess long-term safety outcomes.