Phillip Matson

The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate/human menopausal gonadotropin in women with a poor ovarian response*†

The present study has demonstrated the usefulness of GH in augmenting buserelin acetate/hMG to stimulate the rate of growth of follicles in women regarded as poor responders. The PR achieved was extremely encouraging in a group of patients whose prognosis was otherwise poor. Further studies are required to confirm these preliminary data.

Does elective cryopreservation of all embryos from women at risk of ovarian hyperstimulation syndrome reduce the incidence of the condition

Objectives To analyse the incidence and factors associated with the ovarian hyper‐stimulation syndrome (OHS) in our IVF/GIFT programme before and after the introduction of a strategy to cryopreserve all embryos from women judged to be at risk.

The fertilization of human oocytes by spermatozoa from men with antispermatozoal antibodies in semen

Seventy-two couples, including 15 with antispermatozoal antibodies in the male partners semen, were studied in a program of in vitro fertilization and embryo transfer. Cases were further subclassified as normospermic or oligospermic and antispermatozoal antibodies were assessed with categorization into the respective human immunoglobulin classes as determined using the indirect immunobead test. The study reveals that fertilization is significantly reduced (P<0.001) only if both IgA and IgG antibodies are present in semen but there is no reduction if either class is present alone. The fertilization rate of oocytes is significantly reduced (P<0.001) by sperm from oligospermic samples, and there is a further reduction in those cases with combined IgA/IgG antispermatozoal antibodies.

Time-lapse deselection model for human day 3 in vitro fertilization embryos: the combination of qualitative and quantitative measures of embryo growth.

OBJECTIVE To present a time-lapse deselection model involving both qualitative and quantitative parameters for assessing embryos on day 3. DESIGN Retrospective cohort study and prospective validation. SETTING Private IVF center. PATIENT(S) A total of 270 embryos with known implantation data (KID) after day 3 transfer from 212 IVF/intracytoplasmic sperm injection (ICSI) cycles were retrospectively analyzed for building the proposed deselection model, followed by prospective validation using an additional 66 KID embryos. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Morphological score on day 3, embryo morphokinetic parameters, abnormal cleavage patterns, and known implantation results. RESULT(S) All included embryos were categorized either retrospectively or prospectively into 7 grades (A+, A, B, C, D, E, F). Qualitative deselection parameters included poor conventional day 3 morphology, abnormal cleavage patterns identified via time-lapse monitoring, and <8 cells at 68 hours postinsemination. Quantitative parameters included time from pronuclear fading (PNF) to 5-cell stage and duration of 3-cell stage. KID implantation rates of embryos graded from A+ to F were 52.9%, 36.1%, 25.0%, 13.8%, 15.6%, 3.1%, and 0 respectively (area under the curve [AUC] = 0.762; 95% confidence interval [CI], 0.701-0.824), and a similar pattern was seen in either IVF (AUC = 0.721; 95% CI, 0.622-0.821) or ICSI embryos (AUC = 0.790; 95% CI, 0.711-0.868). Preliminary prospective validation using 66 KID embryos also showed statistically significant prediction in Medicult (AUC = 0.750; 95% CI, 0.588-0.912) and Vitrolife G-Series (AUC = 0.820; 95% CI, 0.671-0.969) suites of culture media. CONCLUSION(S) The proposed model involving both qualitative and quantitative deselection effectively predicts day 3 embryo implantation potential and is applicable to all IVF embryos regardless of insemination method by using PNF as the reference starting time point.

Clinical significance of intercellular contact at the four-cell stage of human embryos, and the use of abnormal cleavage patterns to identify embryos with low implantation potential: a time-lapse study

OBJECTIVE To investigate the clinical significance of intercellular contact point (ICCP) in four-cell stage human embryos and the effectiveness of morphology and abnormal cleavage patterns in identifying embryos with low implantation potential. DESIGN Retrospective cohort study. SETTING Private IVF center. PATIENT(S) A total of 223 consecutive IVF and intracytoplasmic sperm injection treatment cycles, with all resulting embryos cultured in the Embryoscope, and a subset of 207 cycles analyzed for ICCP number where good-quality four-cell embryos were available on day 2 (n = 373 IVF and n = 392 intracytoplasmic sperm injection embryos). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Morphologic score on day 3, embryo morphokinetic parameters, incidence of abnormal biological events, and known implantation results. RESULT(S) Of 765 good-quality four-cell embryos, 89 (11.6%) failed to achieve six ICCPs; 166 of 765 (21.7%) initially had fewer than six ICCPs but were able to establish six ICCPs before subsequent division. Embryos with fewer than six ICCPs at the end of four-cell stage had a lower implantation rate (5.0% vs. 38.5%), with lower embryology performance in both conventional and morphokinetic assessments, compared with embryos achieving six ICCPs by the end of four-cell stage. Deselecting embryos with poor morphology, direct cleavage, reverse cleavage, and fewer than six ICCPs at the four-cell stage led to a significantly improved implantation rate (33.6% vs. 22.4%). CONCLUSION(S) Embryos with fewer than six ICCPs at the end of the four-cell stage show compromised subsequent development and reduced implantation potential. Deselection of embryos with poor morphology and abnormal cleavage revealed via time-lapse imaging could provide the basis of a qualitative algorithm for embryo selection.

Within-laboratory and between-laboratory variability in the measurement of anti-müllerian hormone determined within an external quality assurance scheme.

Ten laboratories in an external quality assurance scheme used the same assay to measure anti-müllerian hormone concentration (Beckman Coulter Gen II) and received twenty serum samples distributed over a 15 month period. The mean bias for all results was only -0.089%, but there was large coefficient of repeatability of 38.8% (sample bias ranged from -37.9% to +54.7%). While each laboratory showed good reproducibility, there was a wide range of average values relative to the consensus value from -24.0% to +22.7%. This between-laboratory variability suggests clinicians should use the same laboratory to avoid problems with result interpretation.

Early pregnancy wastage after gamete manipulation

Summary. The outcome of 1034 pregnancies in women who conceived after referral for infertility management in seven treatment groups is detailed. The mean early pregnancy wastage (before 20 weeks gestation) was 27% and ranged from 18% after AID (artificial insemination by donor semen) to 33% after IVF‐ET (in‐vitro fertilization and embryo transfer). These differences were not due to maternal age which was similar in all groups (means between 29.7 and 32.7 years). Excluding the AID group, there was a high rate of ectopic pregnancy which was significantly higher after GIFT (gamete intrafallopian transfer) and was only partly related to underlying tubal disease. Blighted ova was the main category of early pregnancy loss and was highest after AIH (artificial insemination by husbands semen). There was a higher rate of biochemical pregnancies after GIFT, PROST (pronuclear stage tubal transfer) and IVF‐ET. Our findings confirm a high pregnancy wastage rate in subfertile women and highlight deficiencies in the sperm separation, gamete handling and IVF/embryo culture techniques.

Assisted conception using buserelin and human menopausal gonadotrophins in women with polycystic ovary syndrome

Objective To compare the outcome of in vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) cycles in women with or without ultrasound features of polycystic ovary syndrome (PCOS).

Time-lapse videography of human embryos: Using pronuclear fading rather than insemination in IVF and ICSI cycles removes inconsistencies in time to reach early cleavage milestones

Time-lapse videography showed that human early cleavage embryos were quicker following intracytoplasmic sperm injection to reach developmental milestones compared to in vitro fertilization when using insemination as the timing start point (t0), due to differences in the time taken for embryos to reach pronuclear fading (PNF). These differences disappeared when PNF was used as t0. Using a biological rather than procedural t0 will allow a unified assessment strategy to be applied to all cycles irrespective of the insemination method.

Time-lapse videography of human oocytes following intracytoplasmic sperm injection: events up to the first cleavage division.

A total of 341 fertilized and 37 unfertilized oocytes from 63 intracytoplasmic sperm injection (ICSI) treatment cycles were included for retrospective assessment using the Embryoscope time-lapse video system. The second polar body (pb2) extrusion occurred at 2.9±0.1 h (range 0.70-10.15 h) relative to sperm injection. All oocytes reduced in size following sperm injection (p<0.05) with shrinkage ceasing after 2h in the unfertilized and at pb2 extrusion in the fertilized oocytes. Pb2 extrusion was significantly delayed for women aged >38 years compared to those <35 years (3.4±0.2 vs. 2.8±0.1, p<0.01) or 35-38 years (3.4±0.2 vs. 2.8±0.1, p<0.01), but timing was not related to the Day 3 morphological grades (1-4) of subsequent embryos (2.9±0.1, 2.9±0.1, 2.8±0.2 and 3.0±0.1; p>0.05 respectively). A shorter time of first cleavage division relative to either sperm injection or pb2 extrusion is associated with both top grade (AUC=0.596 or 0.601, p=0.006 or 0.004) and usable embryos (AUC=0.638 or 0.632, p=0.000 respectively) on Day 3. In summary, (i) pb2 of human oocytes extrudes at various times following sperm injection, (ii) the timing of pb2 extrusion is significantly delayed when female age >38 years, but not related to subsequent embryo development, (iii) all human oocytes reduce in size following sperm injection, (iv) completion of pb2 extrusion in the fertilized oocytes is a pivotal event in terminating shrinkage of the vitellus, and (v) time to first cleavage division either from sperm injection or pb2 extrusion is a significant predictive marker for embryo quality on Day 3.