Cancer and male infertility: Gamete intra-Fallopian transfer or in-vitro fertilization after failed ovarian stimulation and intrauterine insemination in unexplained infertility?

A prospective randomized study was designed to compare gameteintra-Fallopian transfer (GIFT) and in-vitro fertilization (IVF)and embryo transfer in the treatment of couples who have failedto conceive after at least three cycles of ovarian stimulationand intrauterine insemination (IUI). A total of 69 couples withprimary unexplained infertility of at least 2 years' durationplus at least three failed cycles of ovarian stimulation andIUI were randomly allocated to either GIFT or IVF/embryo transfer.The clinical pregnancy rate was 34% after GIFT treatment and50% after IVF/embryo transfer. This difference was not statisticallysignificant. The twin rate in the IVF/embryo transfer groupwas higher than in the GIFT group (53 versus 17%, P = 0.005).We conclude that patients with unexplained infertility and failedovarian stimulation and IUI can still achieve encouraging pregnancyrates with IVF/embryo transfer or GIFT. Since IVF/embryo transferis the least invasive of the two procedures and may yield diagnosticinformation, we would favour this therapy; however, the numberof embryos transferred should be reduced to two to reduce therisk of twin pregnancy.     

Timed oocyte collection in an assisted conception programme using GnRH analogue

Three-hundred-and-twenty-five patients on an assisted conception programme underwent 378 cycles of oocyte retrieval (OPU) following ovarian stimulation using a GnRH analogue and human menopausal gonadotrophins (HMG), a regimen which allows programmed cycles and delayed oocyte retrieval. Eighteen cycles were excluded (failed OPU in three and failure of fertilization in 15). In 360 cycles, patients completed their treatment with either in-vitro fertilization/embryo transfer (IVF/ET) (116) or gamete intra-Fallopian transfer (GIFT) (244), of which 241 took place at the normal time and 119 were delayed for 24 h or more to avoid weekend operating. The overall pregnancy rate per OPU was 29.5%, with the IVF group being 24.1% and the GIFT group being 32.8%. In the group of patients in whom OPU was delayed, the pregnancy rate was significantly higher in each sub-group than in the corresponding non-delayed sub-group (overall, 37.0 versus 25.7%; IVF/ET, 38.5 versus 16.9%; GIFT, 36.3 versus 31.1%). There was a significantly higher number of oocytes collected, gametes/embryos transferred in the group whose OPU had been delayed. In patients receiving GnRH analogue and HMG for ovarian stimulation, delaying oocyte retrieval is not harmful, may result in an improved outcome and allows OPU to be performed on routine operating lists. This facility, together with the improved pregnancy rates associated with this protocol of ovarian stimulation should improve the cost-effectiveness of assisted conception programmes.     

Endocrinology: High ovarian response in Yoruba African women during ovulation induction for assisted conception

Fertile Yoruba women from western Nigeria have a much higherincidence of naturally conceived multizygotic twin and tripletpregnancies than Caucasians. The objective of the present studywas to determine whether there are differences between infertileYoruba and Caucasian women in terms of ovarian response in stimulatedcycles for assisted conception. A total of 11 Yoruba women werescheduled for 14 in-vitro fertilization (IVF) and one gameteintra-Fallopian transfer (GIFT) cycles from 1990 to 1992. TheCaucasian group consisted of 209 women scheduled for 213 IVFand 22 GIFT cycles during the same period. Buserelin, 500 µgsubcutaneously daily, was started in the mid-luteal phase toachieve pituitary desensitization. Ovarian stimulation was withvariable amounts of menopausal gonadotrophins. Human chorionicgonadotrophin (HCG) was given to trigger the ovulatory process.The Yoruba and Caucasian groups were similar in age and bodyweight, but significantly more Yorubas (45 versus 11% P <0.005) had ultrasound features of polycystic ovary syndrome(PCOS). The serum oestradiol concentration (3024 versus 2058pg/ml; P < 0.05) and number of follicles >14 mm in diameter(15.5 versus 9.5; P < 0.05) on the day of HCG were higherin the Yoruba group. The ovarian hyperstimulation syndrome (OHSS)was also more prevalent in the Yoruba group (20 versus 5% P< 0.05). No difference was found in clinical pregnancy orembryo implantation rates. These results show a higher tendencytoward exaggerated ovarian response in infertile Yoruba thanCaucasian women, associated with a higher prevalence of PCOS.The risk of developing symptomatic OHSS is higher in Yorubawomen.     

Relationship between the threshold of ovarian sensitivity to human menopausal gonadotrophin stimulation and in-vitro fertilization treatment outcome

In a retrospective study of 813 oocyte retrieval–embryotransfer cycles in women with normal follicle stimulating hormoneand luteinizing hormone concentrations, we sought to investigatethe relationship between the amount of human menopausal gonadotrophin(HMG) used for ovarian stimulation and treatment outcome. Patientswere divided into three groups: group A patients (495 cycles)required <40 ampoules of HMG and had a predicted probabilityfor pregnancy of 25% per embryo transfer; group B patients (165cycles) required 41–77 ampoules per cycle, with a predictedprobability rate for pregnancy of 5–25% per embryo transfer;and group C patients (153 cycles) required >77 ampoules ofHMG and the predicted probability for pregnancy was <5% perembryo transfer. Groups C and A differed significantly (P <0.005). The mean oestradiol concentration on the day of HCGadministration in group C was 6412 pmol/l, and the mean numberof eggs retrieved was seven. The highest success rates werefound when up to 2.5 ampoules of HMG were required for eachegg or 4.4 ampoules for each embryo. The lowest rates were obtainedwhen >4.8 ampoules of HMG were necessary for each oocyteor >9.6 ampoules for each embryo (P < 0.005). We identifieda group of infertile patients who required excessive amountsof HMG to achieve a fair degree of steroidogenesis, number ofeggs and number of embryos but who had very low pregnancy rates.Although all other relevant parameters were normal, this mayhighlight the beginning of ovarian–gamete insufficiencybefore the basic hormonal status is affected. In cases of repeatedfailure, oocyte donation should be considered.     

A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization

The outcome of in-vitro fertilization and embryo transfer (IVF—ET)was compared in 76 patients with polycystic ovaries (PCO) diagnosedon pre-treatment ultrasound scan, and 76 control patients whohad normal ovaries and were matched for age, cause of infertilityand stimulation regimen. Despite receiving significantly lesshuman menopausal gonadotrophin (HMG), patients with PCO, ascompared with controls, had significantly higher serum oestradiollevels on the day of human chronic gonadotrophin administration(5940 ± 255 versus 4370 ± 240 pmol/1, P < 0.001),developed more follicles (14.9 ± 0.7 versus 9.8 ±0.6, P < 0.001) and produced more oocytes (9.3 ± 0.6versus 6.8 ± 0.5, P = 0.003). However, fertilizationrates were reduced in the PCO patients (52.8 ± 3.4% versus66.1 ± 3.4%, P = 0.007). There was no significant differencein cleavage rates. The pregnancy rate/embryo transfer was 25.4%in the PCO group and 23.0% in the group with normal ovaries.There were three high order multiple pregnancies in the PCOgroup compared with none in the group with normal ovaries. Ofthe PCO patients, 10.5% developed moderate/severe ovarian hyperstimulationsyndrome (OHSS) compared with none of the controls (P = 0.006).Patients with and without PCO undergoing IVF have comparablepregnancy and livebirth rates. However, it is important to diagnosePCO before ovarian stimulation is initiated as these patientsare more likely to develop moderate or severe OHSS following1VF—ET.     

Factors associated with fractured zonae pellucidae in an in-vitro fertilization programme

Oocytes with fractured zonae pellucidae (FZP) were recoveredin 43% of cycles in our programme of in-vitro fertilization(IVF) and embryo transfer. Amongst all the recovered oocytesthere were 16% FZP oocytes, in which fertilization was precluded.The mean number of punctured follicles and the success rateof oocyte recovery were significantly higher in cycles yieldingoocytes with fractured zonae compared with cycles yielding onlyoocytes with intact zona pellucida oocytes. A damaged zona wasfound only in healthy mature oocytes and its occurrence wasrelated to the size of the syringe used for follicular aspiration(6.6 versus 20.1% with 10- or 20-ml syringes, respectively,P < 0.001), and not to the form of ovarian stimulation orfollicular characteristics. The proportion of cleaved embryosafter the insemination of oocytes with intact zonae was lowerin patients also yielding oocytes with fractured zonae (74 versus86%, P < 0.001); however, the pregnancy rates after embryoreplacement were the same in both groups. We conclude that thetechnique used for follicle puncture may damage the integrityof zonae pellucidae of healthy mature oocytes. This phenomenonwas estimated to be responsible for {small tilde}15% of failures(16 versus 19 pregnancies per 100 cycles) in our IVF programme.     

Endocrinology: Prospective randomized study of clomiphene citrate and gonadotrophins versus goserelin and gonadotrophins for follicular stimulation in assisted reproduction

We performed a prospective randomized study of goserelin, along-acting gonadotrophin-releasing hormone agonist (GnRHa)and human menopausal gonadotrophin (HMG) versus clomiphene citrateand HMG for follicular stimulation in assisted reproductionto investigate whether the use of this GnRHa provides a clearadvantage in terms of pregnancy per treatment cycle in unselectedpatients, who entered a first trial of assisted reproduction.From a retrospective analysis comparing the two stimulationprotocols, a relative increase of the pregnancy rate per cycleof 50% was anticipated. To detect this difference with a powerof 90%, 300 patients had to be included. The main prognosticfactors affecting the outcome of assisted reproduction wereequally divided among the two groups by a minimization procedure.The pregnancy rates per cycle were significantly better in thegoserelin/HMG group than in the clomiphene citrate/HMG group,both for all procedures of assisted reproduction combined (36.8versus 24.5%; P < 0.02) and for the main procedure of in-vitrofertilization (IVF) (37.0 versus 23.5%; P < 0.02). Differencesin pregnancy rates per oocyte retrieval and per embryo transferwere less pronounced (37.8 versus 30.8%; P = 0.40 and 44.4 versus36.8%; not significant). On the other hand, stimulation withgoserelin/HMG was associated with a higher number of ampoulesof HMG (44.9 versus 9.9; P < 0.0001), a longer duration ofstimulation (11.2 versus 8.7 days; P < 0.0001) and an incidenceof ovarian stimulation of 4.5% (7/154) versus 0% in the clomiphenecitrate/HMG group. Goserelin was well tolerated and proved tobe very reliable as an adjunct of follicular stimulation inassisted reproduction. The main determinants of the higher efficacyof goserelin/HMG in assisted reproduction were the virtual absenceof cancellation of the cycle and the increased number of oocytes.     

Ovary and Ovulation: Contralateral selection of dominant follicle favours pre-embryo development

Ovulation was studied using vaginosonography in a total of 410natural cycles of 123 women undergoing infertility treatment[267 intrauterine insemination (IUI) cycles of 103 women and143 in-vitro fertilization (IVF) cycles of 50 women]. None ofthe women received ovarian stimulation. Each follicle was measureddaily from 14 mm in diameter until formation of corpus luteumor oocyte retrieval. Contralateral ovulation as compared withthe preceding cycle occurred in 57% of the 410 cycles. Contralateralovulations occurred in 72% of cycles with a follicular phase<13 days. In cycles with a follicular phase of >14 days,ovulations occurred at random. The length of follicular phasein contralateral ovulation cycles (15.2 ± 3.2 days) wassignificantly (P < 0.05) shorter than that of ipsilateralovulation cycles (15.8 ± 2.8). During the 57% contralateralovulations in 143 IVF cycles, the rates of oocyte retrieval(89%), fertilization (69%), cleavage (90%) and embryo transfer(56%) were significantly higher than those of ipsilateral ovulations(69, 51, 64 and 23% respectively). The pregnancy rate of contralateralovulations (9%) was also higher, though not significantly, thanthat of ipsilateral ovulations (3%), although the pregnancyrates per transfer were similar (16 and 14% respectively). Thetotal pregnancy rate of both IUI and IVF was higher in contralateralthan in ipsilateral ovulation cycles (8.1 and 4.0% respectively).The dominant follicles in contralateral ovulation cycles showedsignificantly higher oestradiol/androstenedlone ratio (P <0.025) and oestradlol/testosterone + androstenedione ratio (P< 0.025), and lower androstenedione (P < 0.05) than thoseof ipsilateral ovulation cycles. There was no significant differencein oestradiol, progesterone and testosterone. These resultsindicate that the dominant follicles in contralateral ovulationcycles are healthier than those of ipsilateral ones. Local intra-ovarianfactors, e.g. from the corpus luteum, may negatively affectthe health of the dominant follicle and the enclosed oocyte.Therefore contralateral selection of the dominant follicle inthe succeeding cycle may favour pre-embryo development. Thechance of conceiving during a natural cycle may be affectedby the site of ovulation in the preceding cycle.     

A randomized study comparing IVF in the unstimulated cycle with IVF following clomiphene citrate

The efficiency of IVF in unstimulated cycles was compared with that following ovarian stimulation with clomiphene citrate in a simple protocol with ultrasound monitoring only. A total of 132 couples with no previous IVF attempts, selected by female age <35 years, indication for intracytoplasmic sperm injection or infertility caused by tubal factor or unexplained infertility were randomized to the two protocols. Randomization yielded two comparable groups. The clomiphene group (68 couples) performed significantly better than the unstimulated group (64 couples) in terms of number of cycles with oocyte harvest (90/111 or 81% versus 65/114 or 57%; chi(2) = 9.21, P < 0.002), embryo transfers per started cycle (59/111 or 53% versus 29/114 or 25%; chi(2) = 18.14, P < 0.0001), live intrauterine pregnancy rate per started cycle (20/111 or 18% versus 4/114 or 4%; chi(2) = 12.42, P < 0.0001), live intrauterine pregnancy rate per embryo transfer (20/59 or 34% versus 4/29 or 14%; chi(2) = 3.96, P = 0.047), but not in terms of implantation rate (22/85 or 26% versus 4/29 or 14%; chi(2) = 1.65). Only two twin pregnancies occurred. Modest side-effects were recorded following clomiphene. Accordingly, a simple clomiphene citrate protocol, but not IVF in unstimulated cycles, seems compatible with the concept of 'friendly IVF', yielding a fair pregnancy rate both per cycle started and per embryo transfer in selected patients. The results do not substantiate any important negative anti-oestrogenic effects of clomiphene.     

Endocrinology: Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial

Two different regimens of luteal support in gonadotrophin hormone-releasinghormone (GnRH) analoguefhuman menopausal gonadotrophin (GnRHa/HMG)-inducedin-vitro fertilization cycles (IVF) were compared in a randomizedclinical trial. After embryo transfer, either vaginal progesteronealone was administered (n=89, P group), or a combination ofvaginal progesterone and human chorionic gonadotrophin (n=87,P/HCG group). The primary aim of this study was to assess theeffect of the different regimens of luteal support on the pregnancyrate. The secondary aim was to compare oestradiol and progesteroneconcentrations in the luteal phase between the two groups, andassess their effect on the pregnancy rate. A clinical pregnancyrate of 15% was found in the P/HCG group in comparison with26% in the P group (odds ratio 0.49; 99% confidence interval:0.18–1.3). The luteal serum oestradiol and progesteronevalues in the P/HCG group were significantly higher when comparedwith the P group on the 6th, 9th and 12th day after oocyte retrieval(Wilcoxon P<0.001). In accordance with the high oestradiolconcentrations, more cases of ovarian hyperstimulation syndrome(OHSS) were found in the P/HCG group. Oestradiol values on the9th day after oocyte retrieval, presumably the day of implantation,appeared to be higher in women who did not become clinicallypregnant. We conclude that vaginal progesterone alone providessufficient luteal support in GnRHa/HMG induced IVF cycles. Thecombination of vaginal progesterone and HCG as luteal supportleads to significant high luteal oestradiol and progesteroneconcentrations. But a high concentration of oestradiol seemsto have a deleterious effect on the implantation process, resultingin a low pregnancy rate.     

Pregnancy: Premature luteinization as detected by elevated serum progesterone is associated with a higher pregnancy rate in donor oocyte in-vitro fertilization

Premature luteinization has been reported to be associated withdecreased pregnancy rates in patients undergoing in-vitro fertilization.However, the detrimental effect created by a pre-aspirationrise in progesterone is difficult to assess since ovarian stimulationaffects both oocyte quality and endometrial receptivity. Therefore,the relationship between premature luteinization and pregnancyrates remains uncertain. To achieve improved control for confoundingvariables, we studied premature luteinization in ovum donorsof proven fertility. A total of 114 consecutive ovum donationcycles using pituitary suppression with a gonadotrophin-releasinghormone agonist followed by gonadotrophin stimulation were examined.Serum progesterone concentration on the day of administrationof human chorionic gonadotrophin (HCG) was > 1.2 ng/ml in29% of patients. Patients were divided into two groups basedon this value. There was a significant increase in clinicalpregnancy rates per embryo transfer in the group with higherprogesterone concentrations (53 versus 25%, P = 0.012), as wellas significantly more oocytes obtained at aspiration (19.6 ±10.4 versus 13.3 ± 5.4, P < 0.001), and significantlyhigher peak serum oestradiol values (3903 ± 1787 versus2453 ± 1232 pg/ml, P < 0.001). There were no significantdifferences between groups due to age, degree of stimulationor the number of embryos transferred. We conclude that prematureluteinization as based on elevated serum progesterone concentrationis a common occurrence in oocyte donors, reflects healthy folliculardevelopment, and is associated with increased pregnancy rates.     

Implantation: Low implantation rate after in-vitro fertilization in patients with hydrosalpinges diagnosed by ultrasonography

The purpose of this study was to assess whether patients withtubal infertility and a hydrosalpinx have a reduced implantationrate after in-vitro fertilization. The study included 741 patientswho had 1190 consecutive oocyte aspirations. The presence orabsence of hydrosalpinges was assessed by transvaginal ultrasonographyon day 2 of all cycles. In 62 patients treated in 104 cyclesa hydrosalpinx was diagnosed, whereas 493 patients treated in813 cycles had no hydrosalpinx and eight patients treated in16 cycles had uncertain hydrosalpinx. The results show thatthe presence of a hydrosalpinx is associated with a reducedpregnancy rate per aspiration (19.2 versus 32.6% P < 0.01),reduced implantation rate (2.9 versus 10.3%, P < 0.0005),reduced delivery rate per aspiration (5.8 versus 20.9%, P <0.0005), reduced delivery rate per embryo transfer (6.6 versus22.8%, P < 0.0005) and increased early pregnancy loss (70versus 36%, P < 0.005). Among 178 patients with unexplainedinfertility or other infertility factors treated with 257 aspirationsthe results were similar to those in patients with tubal infertilitywithout a hydrosalpinx. In conclusion, the presence of a hydrosalpinxdoes not impair the number of embryos transferred but seemsto impair the implantation process. We hypothesize that thismay be due to leakage of fluid into the uterine cavity whichmay disturb the receptivity of the endometrium and/or the developingembryos.     

Infertility: In-vitro fertilization in completely natural cycles

Our objective was to assess the efficacy of in-vitro fertilization(IVF) in natural ovarian cycles in couples with tubal and unexplainedinfertility. A prospective study design was used. A total of39 fully investigated couples, who were patients at the ReproductiveMedicine Unit, St Michael's Hospital, Bristol, UK, took part;they were diagnosed with either tubal disease (n = 26) or unexplainedinfertility (n = 13). Procedures involved daily capillary bloodsampling, daily vaginal ultrasonography and vaginal oocyte recoveryunder sedation at mid-cycle. The main outcome measures werefertilization, implantation and pregnancy rates. Although moreof the women with tubal disease were parous, there were no othersignificant differences between the two groups. The 39 coupleswith infertility of tubal or unexplained aetiology had 79 cyclesof IVF in otherwise completely natural cycles. The overall fertilizationrate was 80% and the implantation rate was 14.0%. A trend wasobserved for higher success rates in women with tubal disease.We conclude that natural cycle IVF and embryo transfer offersan acceptable chance of pregnancy and an opportunity for thein-depth investigation of follicular and ovarian function incouples with defined causes of infertility. The possibly lowersuccess rate in women with unexplained infertility warrantsfurther study of follicular function and endocrinology.     

Autoimmune disorders: another possible cause for in-vitro fertilization and embryo transfer failure

This study was undertaken to investigate the role of autoantibodiesin association with in-vitro fertilization (IVF) and embryotransfer failure. Anticardiolipin, lupus anticoagulant, anti-deoxyribonucleicacid and antinuclear antibody, rheumatoid factor and antithyroidantibody concentrations were measured. The study group comprised50 IVF patients with three or more previously failed cyclesafter embryo transfer. The control group comprised 80 computer-matchedwomen: 40 who had conceived and delivered following three orless IVF and embryo transfer cycles, and 40 who were healthynulligravidas. The incidence of autoantibodies in the studygroup was 22.0%, compared with 2.5% in the IVF control group(P < 0.05) and 7.5% in the nulligravida group (P < 0.05).In the study group, no statistical difference was found betweenthe patients with unexplained infertility and those with mechanicalinfertility (23.0 and 20.8% respectively). The high occurrenceof autoantibodies found in patients who failed at least threeIVF and embryo transfer cycles could imply that these autoantibodiesmay be one of the possible causes of IVF failure in either mechanicalor unexplained infertility. Further investigations are requiredto indicate the autoantibody profile as part of the work-upafter three or more failed IVF and embryo transfer attempts.     

Implantation: Variations in concentrations of the major endometrial secretory proteins (placental protein 14 and insulin-like growth factor binding protein-1) in assisted conception regimes

We have previously shown that placental protein 14 (PP14) concentrationswere depressed in two pregnancies that followed down-regulationof the anterior pituitary and exogenous hormone support priorto a frozen—thawed embryo transfer. We now report on amore comprehensive series of pregnancies following this formof treatment, in-vitro fertilization (IVF) and natural cyclefrozen—thawed embryo transfer. Serum specimens were analysedfor PP14 and insulin-like growth factor binding protein-1 12days after embryo transfer and at 7 weeks gestation. At 12 daysafter embryo transfer, the mean serum PP14 concentrations inthe IVF and natural cycle were significantly higher in thosewho conceived than those who did not (82 versus 23 and 107 versus39 µg/l respectively, P < 0.001). Although the meanPP14 concentration in the hormone-supported pregnant patientswas higher than in the non-pregnant patients, this had not reachedstatistical significance 12 days after embryo transfer (49 versus31 µg/1). By 7 weeks gestation the PP14 concentrationsin the hormone-supported pregnant patients were significantlyhigher than in the non-pregnant patients (152 versus 31 µg/1,P < 0.001). However, the PP14 concentrations for hormone-supportedpregnant patients were significantly lower (P < 0.001) thanthose for pregnant IVF or natural cycle patients at 7 weeksgestation (152, 777 and 660 µg/l respectively). The PP14concentrations in the pregnant patients, although lower thanthose in IVF and natural cycle pregnancies, were higher thanthose previously reported in ovarian failure and Turner's syndromeovum donation cycles. Patients treated by down-regulation andexogenous hormones had significantly higher serum IGFBP-1 concentrationsthan IVF and natural cycle patients at 7 weeks gestation (P0.01); mean concentrations 107, 58 and 43 µg/l respectively).Elevated IGFBP-1 concentrations may influence the rise in PP14concentrations in these patients.     

Does laparoscopic ovarian diathermy affect the outcome of IVF-embryo transfer in women with polycystic ovarian syndrome? A retrospective comparative study

Controlled ovarian stimulation for IVF and embryo transfer and outcome parameters were compared retrospectively in 31 women with clomiphene-resistant polycystic ovarian syndrome (PCOS). Of these women, 15 had previously undergone laparoscopic ovarian diathermy before IVF (group A, total 22 cycles) and 16 had not had surgical treatment (group B, total 24 cycles). No statistically significant differences were observed in the number of oocytes retrieved, although the number of embryos available for transfer was significantly higher in group B (7.1 +/- 3.8 versus 4.6 +/- 2.7, P < 0.01). The clinical pregnancy rate per embryo transfer appeared to be higher in group B (63.2 versus 41.2%), as did the miscarriage rate (66.7 versus 28.6%), giving an apparent improved ongoing pregnancy rate per embryo transfer in group A (29.4 versus 10.5%), but this was not statistically significantly different. The incidence of severe ovarian hyperstimulation syndrome (OHSS) was apparently higher in group B (4.2 versus 0%), but this difference was not statistically significant. No cases of severe OHSS were seen in group A. Ovarian diathermy does not appear to have a deleterious effect on controlled ovarian stimulation, and the outcome of IVF-embryo transfer may be beneficial in decreasing the risk of severe OHSS and improving the ongoing clinical pregnancy rate.     

Implantation: Embryo score to predict implantation after in-vitro fertilization: based on 957 single embryo transfers

The purpose of this study was to devise an embryo score to predictthe likelihood of successful implantation after in-vitro fertilization(IVF). Unlike most studies dealing with the influence of embryostage and morphology on pregnancy, our study was based on singlerather than multiple embryo transfers. A total of 957 singleembryo transfers were carried out. No delivery was obtainedafter any of the 99 transfers using 1-cell embryos or embryosobtained after delayed fertilization. In the remaining 858 transfers,the embryos had cleaved. Higher pregnancy rates were obtainedwith embryos displaying no irregular cells (11.7 versus 6.9%;P < 0.01) and embryos displaying no fragmentation (11.5 versus8.1%; P < 0.05). The 4-cell embryos implanted 2-fold moreoften than embryos with more or less cells (15.6 versus 7.4%;P < 0.01). Based on these observations, we devised a 4-pointembryo score in which embryos are assigned 1 point each if they(i) are cleaved, (ii) present no fragmentation, (iii) displayno irregularities, and (iv) have four cells. Both pregnancyrate and take home baby rate were significantly correlated withembryo score. Each point of this score corresponds to a 4% increasein pregnancy rate. Interestingly, pregnancy rate was significantlylower in women aged >38 years (8.2 versus 11.4%; P < 0.05),even though embryo quality was similar regardless of age. Singleembryo transfer allowed us to define a simple and useful embryoscore to choose the best embryo for transfer to optimize IVFand embryo transfer outcome. The use of this embryo score coulddecrease multiple pregnancies after multiple embryo transfers.     

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization*

The adverse effect of raised luteinizing hormone (LH) concentrationson reproductive outcome suggests that exogenous LH administrationfor ovarian stimulation may not be desirable. The aim of thisstudy was to compare the clinical pregnancy rates between folliclestimulating hormone (FSH) and human menopausal gonadotrophin(HMG) used in in-vitro fertilization (IVF) cycles. A total of232 infertile patients, with a mean duration of infertilityof 67.1 ± 32.9 months, were selected for IVF (femaleage <38 years, FSH <15 IU/1, and total motile sperm count>5x10⁶). A short (flare-up) protocol with daily leuprolideacetate was followed randomly from day 3 with FSH (n = 115)or human menopausal gonadotrophin (HMG; n = 117), at an initialdose of two ampoules per day. A maximum of three embryos wastransferred, and the luteal phase was supported with four dosesof HCG (2500 IU). No differences were observed between the twogroups in any of the cycle response variables except fertilizationrates per oocyte and per patient, both of which were significantlyhigher with FSH. Clinical pregnancy rates per cycle initiated,per oocyte retrieval and per embryo transfer were 19.1, 21.0and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectivelyfor HMG. Whilst these differences were not statistically significant,the results of this interim analysis suggest that HMG may beassociated with a lower clinical pregnancy rate than FSH.     

The value of IVF-ET in patients undergoing treatment by the GIFT procedure

In patients undergoing the gamete intra-Fallopian transfer (GIFT)procedure, a prospective study was perfonned to establish thepredictive value of attempting in-vitro fertilization (IVF)using extra oocytes obtained at laparoscopy and also the valueof transferring the resulting embryo(s), in conjunction withGIFT, in the same treatment cyde. The GIFT procedure was performedin 50 treatment cycles involving 43 patients, of whom 20 haveachieved clinical pregnancy with an overall success rate of40% per treatment cycle. In 38 of these patients, one or moreextra oocytes were available and an attempt was made in eachcase to fertilize them in vitro. When fertilization failed tooccur in vitro, the chances of pregnancy were significantlyreduced (9.1%). In patients for whom IVF of extra oocyte(s)was successful, there was no significant difference In the pregnancyrate whether embryo transfer was performed or not (54 and 57.1%,respectively). The success rate was also influenced by the numberof oocytes collected rather than the number of oocytes/embryostransferred. Therefore these results suggest that IVF of extraoocytes is a good indicator of in-vlvo fertilization and thatIf extra embryos are obtained they should be cryopreserved.     

Fertilization and early embryology: Prolonged sperm-oocyte exposure and high sperm concentration affect human embryo viability and pregnancy rate

A reduced time interval of oocyte exposure to spermatozoa wasinvestigated to assess whether it could enhance oocyte developmentand improve embryo viability, especially in cases of male factorinfertility. A total of 167 patients were included in a prospectiverandomized study. They were randomly allocated to two majorstudy groups, A (n = 85) and B (control group; n = 82). Theoocytes from group A patients were exposed to spermatozoa foronly 1 h; those from group B were exposed for 16 h. The twostudy groups were then subdivided according to semen qualityfor further analysis of the results. Significantly higher percentageswere obtained in group A than in group B in terms of the fertilizationrate (74 versus 68%, P < 0.025), cleavage rate (53 versus41%, P < 0.005), pregnancy rate (27 versus 12%, P < 0.05)and implantation rate (11 versus 6%, P < 0.05). In addition,an increased fertilization rate was achieved in oocytes exposedto male factor spermatozoa for only 1 h compared with the conventionalincubation period (78 versus 65%, P < 0.01). Advanced cellularstages (55 versus 41%, P < 0.02) and higher implantationrates (13 versus 4%, P < 0.05) were attained in the subgroupwhose oocytes were exposed to normal spermatozoa for 1 h comparedwith the male factor spermatozoa with the standard culture interval.The higher fertilization rates, enhanced embryo developmentand viability achieved in group A indicate that prolonged exposureof oocytes to high concentrations of spermatozoa is detrimental,decreasing sperm-oocyte interaction and subsequent embryo implantation,particularly in male factor patients.