Assessment of ovarian reserve - should we perform tests of ovarian reserve routinely?

Sir, We read with much interest the article by Abha Maheshwari etal. (2006), in which they examined the predictive power     

The importance of egg and sperm factors in predicting the likelihood of pregnancy from gamete intrafallopian transfer

The relative contribution of factors affecting the probability of pregnancy from gamete intrafallopian transfer was estimated using data from 218 cycles performed in San Antonio, Texas, and Orange, California. Mature eggs, all of which contained an expanded cumulus, were subclassified according to the corona radiata; those with a starburst corona were considered the most fully mature. Sixty-two clinical pregnancies were established, representing a pregnancy rate of 28.4%. Excluding 49 cases of male factor infertility, the pregnancy rate was 34.9%. Pregnancy rates were not significantly different according to age, cause of female factor infertility, parity, duration of infertility, stimulation protocol, or estradiol level. The only variables having a strong association with pregnancy were sperm and egg parameters. Sperm motility and morphology were statistically more important than sperm density. Based on odds ratios calculated from multiple logistic analysis, pregnancy was 3.80 times more likely if three or more fully mature eggs were transferred, 0.34 times as likely if motility were less than or equal to 30%, and 0.22 times as likely if normal morphology was less than or equal to 50%, controlling for other egg and sperm factors. If all egg and sperm factors in a given cycle were unfavorable, the probability of pregnancy estimated by the logistic model was 4%, whereas if all were favorable the probability of pregnancy in that cycle was 59%.     

Non-surgical expulsion of non-viable early pregnancy: a new application of RU 486

As an alternative to dilatation and curettage or expectant management, a single oral dose of 600 mg RU 486 was given to 3 women after failure of early pregnancy after in vitro fertilization and embryo transfer (IVF- ET) or gamete intra-Fallopian transfer (GIFT). In these women when early pregnancies are lost, missed abortions may endure because of continued progesterone release by the corpus luteum causing sustained hCG production by remaining trophoblast tissue. These 3 cases experienced fetal demise at 40, 38 and 28 days gestation. RU-486 was given orally on Days 53, 55 and 45, respectively, resulting in passage of the gestational sac within 2-3 days in all cases. The women experienced light spotting for 2 days, or bleeding for 1 week. Their menses reappeared within 1 month. This non-invasive approach was welcomed by the patients as a psychological relief.     

Active immunisation with RAMA does not provide protective immunity against Plasmodium yoelii challenge despite its association with protective responses in endemic populations

The rhoptry associated membrane antigen (RAMA) of Plasmodium falciparum has been proposed as a potential candidate for inclusion in a multivalent subunit vaccine against malaria. Previous studies have found that the RAMA gene is refractory to genetic deletion in vitro and is conserved in a range of clinical isolates. Importantly, two independent studies demonstrated that antibodies against the C-terminal region of RAMA are associated with immunity in endemic populations of both Asia and Africa. However, there is presently no direct evidence that anti-RAMA immune responses have a demonstrable anti-parasitic effect either in vitro or in vivo. In this study we used an in vitro invasion inhibition assay and the Plasmodium yoelii mouse model of infection to evaluate the potential of RAMA as a vaccine candidate. Our results demonstrate that anti-PfRAMA antibodies have only a weak inhibitory effect on P. falciparum invasion in vitro. Immunisation with recombinant PyRAMA protein did not protect mice against a lethal P. yoelii infection and did not boost the level of protection induced by a known protective antigen, merozoite surface protein 4/5. Taken together, these data do not support RAMA as a priority vaccine candidate.     

Apical location of a novel EGF-like domain-containing protein of Plasmodium falciparum

Using bioinformatics analyses of the unfinished malaria genome sequence, we have identified a novel protein of Plasmodium falciparum that contains two epidermal growth factor (EGF)-like domains near the C-terminus of the protein. The sequence contains a single open reading frame of 1572bp with the potential to encode a protein of 524 residues containing hydrophobic regions at the extreme N- and C-termini which appear to represent signal peptide and glycosylphosphatidylinositol (GPI)-attachment sites, respectively. RT-PCR analysis has confirmed that the novel gene is transcribed in asexual stages of P. falciparum. Antibodies to the EGF-like domains of the novel protein are highly specific and do not cross-react with the EGF-like domains of MSP1, MSP4, MSP5 or MSP8 expressed as GST fusion proteins. Antisera to the C-terminal fragments react with two bands of 80 and 36kDa in P. falciparum parasite lysates whereas antisera to the most N-terminal fusion protein only recognises the 80kDa band, suggesting that the novel protein may undergo processing in a similar way to MSP1 and MSP8, but with fewer cleavage events. Immunoblot analysis of stage-specific parasite samples reveals that the protein is present in trophozoites, schizonts and in isolated merozoites. The protein partitions in the detergent-enriched phase after Triton X-114 fractionation and is localised to the surfaces of trophozoites, schizonts and free merozoites in an apical distribution. Based on the accepted nomenclature in the field we now designate this protein MSP10. We have shown that the MSP10 fusion proteins are in a conformation that can be recognised by human immune sera and that there is very limited sequence diversity in an approximately lkb region of MSP10, encompassing the two EGF-like domains. A sequence similar to MSP10 can be identified in the available P. yoelii genomic sequence, offering the possibility of ascertaining whether this novel protein can induce host protective responses in an in vivo model.     

Further improvement in IVF outcome may need more than consistency in ovarian stimulation

It is agreed that reliability of hormonal products, starting with recombinant technology, has improved uniformity of ovarian response to a specified dosage, and that this has resulted in better pregnancy rates. Nevertheless, IVF cycle cancellation rate has not experienced a substantial decline in the last 5-10 years. We feel that further improvement will be more likely to be achieved once we gain better understanding of factors intrinsic to oocyte biology, such as oocyte ageing and oocyte depletion.     

Relationship between time period after vasectomy and the reproductive capacity of sperm obtained by epididymal aspiration

BACKGROUND: It is not well defined whether the elapsed time after vasectomy has any influence on the outcome of IVF-ICSI using epididymal sperm. We analysed retrospectively the results of 151 ICSI cycles in which sperm of vasectomized men were used at different time periods after vasectomy. METHODS: Oocytes were obtained after a desensitizing ovarian stimulation protocol using GnRH agonist in association with recombinant FSH and HCG. Sperm were retrieved by percutaneous epididymal sperm aspiration. The cycles were split into three groups: < or =10 years after vasectomy (group 1, n = 47), 11-19 years after vasectomy (group 2, n = 79), and > or =20 years after vasectomy (group 3, n = 25). RESULTS: As might be expected, the mean age of men differed in the three groups (group 3 > group 2 > group 1), and the mean age of the women was also significantly higher in group 3 than in groups 1 and 2, although no differences were described between groups 2 and 3. All other laboratory and clinical parameters were similar in the three groups. Ongoing pregnancy and implantation rates (34, 25, 8% and 22, 15, 6% respectively) decreased significantly from group 1 to group 3. CONCLUSION: Pregnancy and implantation rates after ICSI with sperm from vasectomized men are negatively correlated with the time interval from vasectomy, which cannot be explained purely by male or female ageing.