Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial.

RESEARCH QUESTION: Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)? DESIGN: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC. RESULTS: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates. CONCLUSION: This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducted.

Conjugating phosphospermines to siRNAs for improved stability in serum, intracellular delivery and RNAi-mediated gene silencing.

siRNAs are usually formulated with cationic polymers or lipids to form supramolecular particles capable of binding and crossing the negatively charged cell membrane. However, particles hardly diffuse through tissues when administered in vivo. We therefore are developing cationic siRNAs, composed of an antisense sequence annealed to an oligophosphospermine-conjugated sense strand. Cationic siRNAs have been previously shown to display gene silencing activity in human cell line (Nothisen et al. J. Am. Chem. Soc.2009). We have improved the synthesis, purification and characterization of oligospermine-oligoribonucleotide conjugates which provide cationic siRNAs with enhanced biological activity. We show data supporting their carrier-free intracellular delivery in a molecular, soluble state. Additional results on the relationship between global charge, uptake and silencing activity confirm the requirement for an overall positive charge of the conjugated siRNA in order to enter cells. Importantly, conjugated siRNAs made of natural phosphodiester nucleotides are protected from nuclease degradation by the oligophosphospermine moiety, operate through the RNAi mechanism and mediate specific gene silencing at submicromolar concentration in the presence of serum.

Successful pregnancy following novel IVF protocol and transmyometrial embryo transfer after radical vaginal trachelectomy.

Radical vaginal trachelectomy in patients with early-stage cervical cancer is an oncologically safe procedure in well-selected patients. Successful pregnancy in a patient with radical vaginal trachelectomy is possible, with two-thirds of pregnancies resulting in live birth. However, it presents a great challenge for assisted reproductive techniques and reproductive medicine in cases with subsequent severe cervical stenosis. This is a report of a 38-year-old patient who underwent radical vaginal trachelectomy at the age of 33 years for early stage (IA2) adenocarcinoma and subsequently presented with infertility due to cervical factors. The patient underwent ovarian stimulation using a novel SMART (Stimulation with Minimal Adverse effects, Retrieval and Transfer)-IVF protocol. As it was impossible to perform transcervical embryo transfer with an almost absent severely stenotic cervical opening, a transmyometrial embryo transfer under ultrasound guidance was performed. This resulted in a successful singleton full-term pregnancy delivered by Caesarean section at gestational age 37 weeks. As far as is known, this is the first reported case of successful pregnancy conceived by IVF with transmyometrial embryo transfer for a patient who had previously undergone radical vaginal trachelectomy.

Successful pregnancy in an ovarian agenesis patient after modified natural cycle IVF oocyte donation.

The recovery of a mature oocyte from a modified natural cycle followed by in-vitro fertilization (nIVF) is an attractive alternative to conventional IVF, involving ovarian stimulation, in the treatment of female infertility. Ovarian agenesis is a rare disorder resulting in primary amenorrhoea and infertility in affected females. A couple sought help for infertility due to ovarian agenesis of the female partner and decided to pursue treatment utilizing oocyte donation. Modified natural-cycle egg retrieval was carried out on the donor; one mature oocyte was retrieved and underwent IVF using a sperm sample from the male partner. A good-quality embryo was transferred, A viable pregnancy was confirmed by ultrasound scan and resulted in the delivery of a healthy baby boy at 36 weeks' gestation. This is the second published report of an ongoing clinical pregnancy and subsequent birth resulting from oocyte donation recovered during a modified natural cycle. The use of less invasive assisted reproduction techniques such as nIVF can be used in oocyte donation cycles successfully.

Reproducibility of first trimester three-dimensional placental measurements in the evaluation of early placental insufficiency.

OBJECTIVE: To evaluate the reproducibility of first-trimester, three-dimensional placental volume and vasculature evaluation by ultrasound in correlation with uterine artery Doppler flow studies. METHOD: We performed a prospective study of a cohort of pregnant women undergoing first-trimester ultrasound examination. Uterine artery Doppler and 3-D power Doppler angiography was performed. Placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated three times by two independent observers using the virtual organ computer-aided analysis (VOCAL) software. Intra- and interobserver reproducibility was evaluated by Spearman's correlation test. All parameters between women with low (< 1.5 multiple of median) (MoM) and high (> 1.5 MoM) uterine artery Pourcelot index (PI) were compared by the Mann-Whitney test. RESULTS: A total of 35 women between 11 and 14 weeks' gestation were recruited, including 26 who underwent uterine artery Doppler and six with elevated uterine artery PI. We found excellent intra- and interobserver reproducibility (R2 > 0.85) for all parameters. Women with elevated uterine artery PI had smaller placental volume, VI, FI, and VFI (P < 0.05). CONCLUSION: 3-D placental volume and vasculature evaluations during the first trimester are reproducible measures that inversely correlate with uterine artery PI.

A randomized cross over trial of tolerability and compliance of a micronutrient supplement with low iron separated from calcium vs high iron combined with calcium in pregnant women [ISRCTN56071145].

BACKGROUND: Prenatal micronutrient combinations with high iron content are associated with high rates of gastrointestinal symptoms. This coupled with nausea and vomiting of pregnancy results in women often discontinuing their multivitamins. A new prescription supplement (PregVit) that separates iron from calcium in two tablets--morning and evening, has lower elemental iron content (35 mg), but results in similar extent of iron absorption when compared to another supplement containing (60 mg) of elemental iron (Materna). The objectives of this study were to compare tolerability and compliance with PregVit vs. a supplement with high iron content (Materna), in pregnant women. METHODS: Randomized, crossover open labeled study in 135 pregnant women attending outpatient clinics in Ontario and Quebec. RESULTS: Use of PregVit was associated with a 30% reduction in constipation rate as compared to Materna. Both products demonstrated similar compliance rates. Compliance of Materna was negatively associated with the severity of nausea and vomiting of pregnancy. No such correlation was found for PregVvit. CONCLUSION: PregVit, a supplement with lower iron content (35 mg), has significantly decreased constipation rates as compared to 60 mg iron--Materna and has similar compliance rates. High iron content in multivitamin supplements is associated with adverse effects in pregnancy.

Spontaneous ovulation rate before oocyte retrieval in modified natural cycle IVF with and without indomethacin.

The objective of this retrospective analysis was to evaluate the number of spontaneous ovulations occurring before oocyte retrieval in natural cycle IVF (nIVF) with and without the use of indomethacin. A total of 121 patients who underwent modified nIVF cycle between December 2003 and July 2006 were included in the study; 171 cycles without indomethacin and 84 cycles with indomethacin, started when the leading follicle reached 14 mm in size, were compared. The number of cycles with ovulation before oocyte retrieval and the number of cycles with no oocytes at retrieval were assessed with and without indomethacin. In addition, the pregnancy rates in the two groups of patients were analysed. There were 28 cycles (16%) in which ovulation occurred before oocyte retrieval in the group where no indomethacin was used and five cycles (6%) in which ovulation occurred before retrieval in the group where indomethacin was used. There was a statistically significant association between premature ovulation and indomethacin, with an odds ratio of 3.8 (95% confidence interval, 1.2-12.3). The oocyte retrieval per started cycle was 64% without indomethacin and 76% with indomethacin (P < 0.04). The clinical pregnancy rate per embryo transfer was 14% without indomethacin and 21% with indomethacin (not significant).

Controlled natural cycle IVF: experience in a world of stimulation.

A total of 134 controlled natural IVF (nIVF) cycles were reviewed retrospectively and compared with 370 stimulated IVF (sIVF) cycles. The clinical pregnancy rate per embryo transfer following nIVF was 27% and 47% in sIVF cycles for patients aged less than 35. However, natural cycle patients could attempt consecutive cycles with much less impact on their lives, both medically and financially. In patients under 35 years of age, the choice of controlled nIVF reduces the cost and risk to the patient, permitting her to have multiple, consecutive attempts, and cumulatively offers a clinical pregnancy rate which approaches that of sIVF. The multiple pregnancy rate in nIVF is significantly reduced compared with sIVF treatment cycles. In patients over 35 years of age the benefits of nIVF were much less evident (clinical pregnancy rate: 8% per embryo transfer) and the opportunity to transfer multiple embryos in these patients seems to be advantageous.

Vasa praevia after IVF: should there be guidelines? Report of two cases and literature review.

The paper gives an illustration and reminder of the risk of problems with placentation resulting from IVF and embryo transfer. Reported here is one neonatal death related to vasa praevia when the condition was not diagnosed antenatally and a neonatal survival when vasa praevia was detected antenatally. A search of the English literature was performed using PubMed for 'vasa praevia and in vitro fertilization'. There were four articles that directly addressed this relationship. Case reports of IVF-embryo transfer pregnancies with vasa praevia and also studies that look at the incidence of vasa praevia in such pregnancies are included in this report. Hence, since vasa praevia is thought to be caused by a disturbed orientation of the blastocyst at implantation, it is probably related to the IVF-embryo transfer procedure. Screening of all IVF-embryo transfer pregnancies with transvaginal sonography and colour Doppler to rule out vasa praevia is recommended in the second trimester.

Ongoing pregnancy after ICSI of frozen-thawed PESA-retrieved spermatozoa and IVF in a controlled natural cycle.

The recovery of a mature oocyte from a natural cycle followed by IVF (nIVF) is an attractive alternative to conventional IVF, involving ovarian stimulation, in the treatment of female infertility. Similarly, surgical recovery of spermatozoa from the epididymis by percutaneous sperm aspiration (PESA) has simplified the treatment of men with obstructive azoospermia. A couple sought treatment for diminished ovarian reserve and male factor infertility using IVF. A mature oocyte was retrieved and was inseminated by intracytoplasmic sperm injection (ICSI), following recovery of spermatozoa by PESA. A good quality embryo was transferred. A viable pregnancy was confirmed by ultrasound scan. A healthy baby boy was delivered naturally at 37 weeks gestation. This study reports the first ongoing clinical pregnancy and subsequent birth resulting from ICSI of spermatozoa retrieved by PESA into an oocyte recovered during a natural cycle. The use of a combination of less invasive assisted reproductive techniques (PESA and nIVF) can overcome barriers to fertility.