Serum inhibin levels in gonadotrophin stimulated in-vitro fertilization/gamete intra-fallopian transfer cycles.

Serum inhibin concentrations of 64 cycles of in-vitro fertilization--embryo transfer (IVF-ET) or gamete intra-Fallopian transfer (GIFT) have been analysed retrospectively. No significant difference was observed in serum inhibin levels of cycles stimulated with buserelin and human menopausal gonadotrophin (HMG) or HMG alone. During the late follicular phase, serum inhibin was higher in cycles resulting in pregnancy than in cycles without a pregnancy (peak values on day +1: 8.3 versus 6.4 IU/ml, respectively). The same difference was found between stimulation cycles resulting in a viable or a non-viable pregnancy (peak values on day +1: 8.3 versus 7.5 IU/ml). However, these differences were not significant. During the early luteal phase, serum inhibin values were similar in these groups of patients. Our results indicate that the use of the gonadotrophin-releasing hormone (GnRH) analogue buserelin, in combination with HMG, for ovarian stimulation does not affect inhibin production by granulosa cells in vivo. The late follicular and early luteal concentrations of serum inhibin have to be considered unsuitable as predictors in IVF/GIFT cycles with respect to pregnancy and pregnancy outcome.     

Will GnRH antagonists provide new hope for patients considered 'difficult responders' to GnRH agonist protocols?

We have assessed the use of cetrorelix, a gonadotrophin releasing hormone (GnRH) antagonist, in conjunction with clomiphene citrate and gonadotrophin in 31 in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) cycles for 25 difficult responders. Group I included 18 poor responders (24 cycles) with no live birth in 23 previous IVF cycles with GnRH agonists. Group II included seven patients (seven cycles) with polycystic ovaries. Thirteen previous IVF/GIFT cycles with GnRH agonists had resulted in one live birth and three of these patients had developed ovarian hyperstimulation syndrome (OHSS). The treatment protocol involved a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections from cycle day 2. Cetrorelix 0.25 mg/day was started when the leading follicle reached 14 mm. The outcome in both groups was favourable compared to previous treatment with GnRH agonists. In group I the abandoned cycle rate was 29 versus 57% (P = 0.06). More oocytes were produced (6.4 versus 4.7 oocytes/cycle) at a lower dose of follicle-stimulating hormone (FSH) (709 versus 1163 IU/oocyte; P = 0.08) and two live births resulted (11.8%). In group II fewer oocytes were produced (10.2 versus 14.5 oocytes/cycle), using a lower dose of gonadotrophin (170 versus 189 IU/oocyte) and resulted in one ongoing pregnancy. No patients experienced OHSS. This report is preliminary and a further controlled randomized study is required.     

Management of failed cycles in an IVF/GIFT programme with the combination of GnRH analogue and HMG

The addition of the gonadotrophin rrleasing hormone (GnRH) agonistBuserelin to human menopausal gonadotrophin/human chorioaicgonadotrophin (HMG/MCG) during ovarian stimulation was evaluatedin 23 cycles of 21 women who previously had unsuccessful IVFtreatments when stimulated with clomiphene-HMG/HCG. No adverseeffects of GnRH-agonist on folliculogenesis were seen. A meannumber of 7.2 oocytes per retrieval was collected in 20 treatmentcycles. Oocytes quality, fertilization and cleavage parameterswere normal. Replacements by gamete intra-Fallopian transfer(GIFT) or IVF took place for 16 patients. Four patients becamepregnant in their treatment cycle, one aborted. For 8 patients18 embryos were cryopreserved, one transfer of a frozen-thawedembryo in a subsequent natural cycle led to a pregnancy. Inadequateluteal phases were constantly observed when supplementationwas omitted. Further study is required to confirm that systematicluteal support improves the pregnancy rate.     

Endometriosis: Comparison among different ovarian stimulation regimens for assisted procreation procedures in patients with endometriosis

The objective of our study was to establish the most adequateovarian stimulation regimen for assisted procreation in endometrioticpatients. It consisted of a retrospective analysis comparingthe use of the gonadotrophin-releasing hormone analogue (GnRHa)buserelin either for 3 months or for 3 weeks and continued withovarian stimulation with human menopausal gonadotrophin (HMG),and the use of clomiphene citrate in association with HMG forin-vitro fertilization (IVF) and embryo transfer, gamete intra-Fallopiantransfer (GIFT) and zygote intra-Fallopian transfer (ZIFT).A total of 145 patients with endometriosis in 174 cycles weredivided into two groups according to the revised American FertilitySociety staging of the disease (group A, stages 1 and 2; groupB, stages 3 and 4). The use of GnRHa significantly increasedthe number of oocytes retrieved. GnRH analogues for 3 monthsgave the highest fertilization rate for groups A and B. Thecleavage, pregnancy and delivery rates, although higher in thegroups treated with analogues, did not reach statistical significance.A higher number of patients had an embryo transfer in the groupstreated with GnRHa (P < 0.05). Treatment with GnRHa for either3 months or for 3 weeks proved to be more efficient than clomiphenecitrate-HMG for assisted procreation procedures in patientswith endometriosis.     

Women with one ovary have decreased response to GnRHa/HMG ovulation protocol in IVF but the same pregnancy rate as women with two ovaries

The study compares the response after gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) stimulation for in-vitro fertilization (IVF) in patients with either one or two ovaries. The study group (group A) included 73 cycles in women who had unilateral oophorectomy before their IVF treatment and the control group (group B) included 988 cycles in women with two ovaries. Tubal disease was the sole cause for infertility in all cases. The two groups were similar in age and parity. The patients with one ovary required more ampoules of HMG (62.9 versus 48.9, P < 0.001), a longer induction period (13.5 versus 12.7, P < 0.01) and had significantly lower oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration (5840 versus 6473 pmol/l, P = 0.035). They yielded fewer follicles (11.2 versus 13.1, P = 0.005), fewer oocytes (7.3 versus 9.1, P = 0.006) and produced fewer embryos (4.4 versus 5.1, P < 0.05). There was no difference in fertilization rate (60 compared with 58%), or pregnancy rate (25.8 compared with 27.1% per oocyte retrieval). Women with only one ovary responded less well to GnRH agonist/HMG stimulation than women who had both ovaries but pregnancy outcome was the same in both groups.      

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.     

Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles

BACKGROUND: The aim of this study was to compare the effect of three different times of onset of luteal phase support on ongoing pregnancy rate in infertile patients undergoing treatment with GnRH down-regulated IVF and embryo transfer (IVF/ET). MATERIALS AND METHODS: All consecutive eligible patients planned to undergo their first IVF treatment cycle were randomly allocated to receive vaginal progesterone as luteal support at three different time points, that is, after HCG administration for final oocyte maturation (HCG group), at the day of oocyte retrieval (OR group) or at the day of ET (ET group). The primary endpoint of this study was ongoing pregnancy rate. RESULTS: A total of 385 women were randomized, 130 were allocated to the HCG group, 128 to the OR group and 127 to the ET group. An ongoing pregnancy rate of 20.8% was found in the HCG group versus 22.7 and 23.6% in the OR group and ET group, respectively. The mean number and quality of the retrieved oocytes and the transferred embryos did not differ. CONCLUSION: Based on this data, an 18% difference in ongoing pregnancy rate between the three different times of onset of luteal phase support in GnRH agonist down-regulated IVF/ET cycles can be refuted. Smaller clinically meaningful differences may be present.     

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.     

The leuprolide flare regime for in-vitro fertilization/gamete intra-fallopian transfer and embryo cryopreservation.

Gonadotrophin releasing hormone agonists (GnRHa) are now well established as adjuvant agents for in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) but several different modes of usage have been proposed. Our experience with 328 cycles of leuprolide used in a flare regime is reviewed. An endocrinologically proven flare effect was associated with a reduction of human menopausal gonadotrophin (HMG) usage (10 versus 16 ampoules) and a lower cycle cancellation/conversion rate (7.4 versus 11.3%). Overall, satisfactory rates of oocyte recovery (93%, mean number of oocytes 7.0), clinical pregnancy (24.4% per oocyte recovery) and pregnancy from frozen/thawed embryo transfers (14%) were achieved. The flare protocol appears to be a satisfactory choice for the majority of subjects but careful monitoring is required to avoid the potential for ovarian hyperstimulation.     

GnRH agonist versus GnRH antagonist in oocyte donation cycles: a prospective randomized study

BACKGROUND: The specific role of LH in folliculogenesis and oocyte maturation is unclear. GnRH antagonists, when administered in the late follicular phase, induce a sharp decrease in serum LH which may be detrimental for IVF outcome. This study was performed to evaluate whether the replacement of GnRH agonist (triptorelin) by a GnRH antagonist (ganirelix; NV Organon) in oocyte donation cycles has any impact on pregnancy and implantation rates. METHODS: A total of 148 donor IVF cycles was randomly assigned to use either a GnRH antagonist daily administered from the 8th day of stimulation (group I) or a GnRH agonist long protocol (group II) for the ovarian stimulation of their donors. The primary endpoints were the pregnancy and the implantation rates. RESULTS: The clinical pregnancy rate per transfer (39.72%, 29/73 versus 41.33%, 31/75) based on transvaginal scan findings at 7 weeks of gestation, the implantation rate (23.9 versus 25.4%) and the first trimester abortion rate (10.34 versus 12.90%) were similar in the two groups. CONCLUSION: In oocyte donation cycles the replacement of GnRH agonist by a GnRH antagonist appears to have no impact on the pregnancy and implantation rates when its administration starts on day 8 of stimulation.     

LH serum levels during ovarian stimulation as predictors of ovarian response and assisted reproduction outcome in down-regulated women stimulated with recombinant FSH

BACKGROUND: There has been much debate about the effect of 'residual' LH levels in normogonadotrophic women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH ovarian stimulation. The aim of this prospective study, where receiver-operating characteristic (ROC) analysis was used, was to assess further the usefulness of serum LH levels as predictors of ovarian response, assisted reproduction treatment outcome, and the outcome of pregnancy when measured throughout the ovarian stimulation period in a large cohort of such assisted reproduction treatment women. METHODS: A total of 246 consecutive women undergoing their first cycle of IVF or ICSI treatment were included in this study. Blood samples for hormone analyses were obtained on day S0 (the day when pituitary suppression was evidenced) and every other day from stimulation day 5 (S5) until the day of hCG injection. RESULTS: LH serum levels throughout ovarian stimulation treatment were similar for cancelled (n =32) versus non-cancelled (n = 214) cycles, non-conception (n = 132) versus conception (n = 82) cycles, and ongoing pregnancy (n = 66) versus early pregnancy loss (n = 16) groups. There was no correlation between LH serum levels in non-cancelled cycles and parameters of ovarian response and assisted reproduction treatment outcome. ROC analysis showed that serum LH concentration during ovarian stimulation was unable to discriminate between cancelled and non-cancelled cycles, conception versus non-conception cycles, or early pregnancy loss versus ongoing pregnancy groups. CONCLUSIONS: Serum LH measurements during ovarian stimulation with recombinant FSH under pituitary suppression in normogonadotrophic women undergoing assisted reproduction treatment cannot predict ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy. Thus, there is little underlying physiological support for the addition of LH in stimulation protocols if daily doses of an appropriate GnRH agonist (leuprolide or triptorelin having lower potency than buserelin) and a step-down regimen of recombinant FSH administration are used.     

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.     

Infertility: The prognosis for assisted conception treatment after unexpected failure of fertilization in vitro: a comparative study

The relative prognosis for further assisted conception treatment(without micro-injection) after initial unexpected failure offertilization in apparently favourable couples undergoing in-vitrofertilization (IVF) treatment was assessed. After their firstcycle of treatment, 481 consecutive couples were grouped accordingto their fertilization (including cleavage) rate per oocyteinto five bands. Proportions of couples proceeding to furthercycles of treatment by IVF or gamete intra-Fallopian transfer(GIFT) and resulting fertilization and pregnancy rates werecompared. Pregnancy rates in the first cycle of treatment weresignificantly related to fertilization rate. The fertilizationrate was zero in 13 couples (3%) and only 1–24% in 18(4%). There were no significant differences between these groupsin the proportions proceeding to further treatment (31, 50%)compared with others (overall 37%, including some treated byGIFT), or in their median fertilization rates (75, 60% comparedwith 67% – IVF cycles only), pregnancy rates (20, 38%of cycles compared with 37% – IVF or GIFT) or birth rates(20, 38% of cycles compared with 31% – IVF or GIFT). Amongstcouples whose initial fertilization rate was 50% there wasno fertilization in 4% of subsequent IVF cycles. We concludethat in couples with well defined favourable conditions, includingtests of sperm function for assisted conception treatment, whohave unexpected failure of fertilization, the prognosis forfurther treatment remains favourable without resort to morecomplex investigations or micro-injection methods. Such failureoccurs infrequently and generally as a random event, and shouldhave no appreciable effect on life-table calculation of cumulativepregnancy and birth rates in this group of patients.     

Infertility: Natural cycles for in-vitro fertilization: cost-effectiveness analysis and factors influencing outcome

Improvements in oocyte culture technique, sperm preparation,oocyte retrieval method and ovarian stimulation regimens haveproduced higher pregnancy rates with in-vitro fertilization(IVF) treatment. However, because ovarian stimulation is expensiveand not without risk, there is increasing interest in the optionof using natural cycles for IVF. This study was performed todocument the experience and outcome in 240 natural cycles. Cancellationoccurred in 28 cycles (12%), and LH surge was observed in 56(23%), leaving 156 (65%) cycles which progressed to oocyte retrieval.No oocytes were retrieved in 26 cycles. Among the successfuloocyte retrievals, the majority yielded one oocyte. There wasno evidence of fertilization in 26 cases, and triploid fertilizationwas observed in 12 cases. Embryos suitable for transfer wereavailable in 92 cycles in which 11 (12%) clinical pregnancieswere confirmed. Despite the high failure rate at each step inthe process, natural cycles are more cost-effective than stimulatedcycles which incur an incremental cost per live birth of $48000. Natural cycles offer a low-cost alternative that may bemore accessible to patients.     

The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women

It has been suggested that the luteinizing hormone (LH) activityof human menopausal gonadotrophin (HMG) preparations used forovarian stimulation in in-vitro fertilization (IVF) may haveadverse effects on reproductive outcome. In the present prospective,randomized trial of 218 infertile couples this notion was investigated.A total of 114 women were treated with Pergonal (HMG group)and 104 with Fertinorm HP (HP-FSH group). The two groups werecomparable with regard to duration of infertility, cause ofinfertility, age and number of previous IVF attempts and allhad normal basal gonadotrophin concentrations before treatmentwas started. A standard hormonal treatment consisting of pituitarydown-regulation with gonadotrophin-releasing hormone analogue(GnRHa) for 14 days starting on cycle day 21, followed by eitherHMG or highly purified follicle stimulating hormone (HP-FSH),three ampoules (225 IU) per day for 7 days, was used in allcases. The daily hormone dose was thereafter individualizedaccording to the ovarian response. A maximum of two pre-embryoswere transferred after 3 days of culture. Luteal support withprogesterone (300 mg per day intravaginally) was used in allcases. Serum concentrations of oestradiol, FSH and LH were measuredon days 1 and 8 of stimulation and on the day of oocyte retrieval.The mean number of days of stimulation, mean number of ampoulesof HMG or HP-FSH used, mean total motile sperm count on theday of oocyte retrieval and mean numbers of oocytes retrieved(13.4 versus 13.7) or pre-embryos transferred (1.8 versus 1.8)were similar for both groups. Significantly (P < 0.05) morecycles in the HP-FSH group (17 = 16%) were cancelled due tocomplete failure of fertilization than in the HMG group (7 =6%). The mean fertilization rate was significantly (P < 0.05)higher in the HMG group (56%) than in the HP-FSH group (50%),and significantly more transferable pre-embryos were obtainedin the HMG than in the HP-FSH group (mean: 4.0 versus 3.2; P< 0.01). Serum hormone concentrations were similar in thetwo groups on stimulation day 1, but differed significantlywith regard to FSH, LH and oestradiol on stimulation day 8.The clinical outcome was similar in the two groups, with anongoing pregnancy rate (>12 weeks of gestation) per startedcycle of 33% in the HMG group and 29% in the HP-FSH group. Theclinical abortion rates were similar(10 and 14%), and the implantationrate was 30% in each group. In conclusion, no detrimental effectof the LH activity of HMG on the clinical outcome of IVF inGnRHa down-regulated normogonadotrophic women was found. Tothe contrary, some beneficial effects of HMG on fertilizationrates and pre-embryo development as compared with HP-FSH weredemonstrated. These effects, as well as the differences in serumhormone concentrations during ovarian stimulation, may be causedby differences in LH content and/or in the composition of FSHisoforms of the HMG and HP-FSH preparations.     

Influence of the duration of the oestradiol rise on the success rate in GnRH analogue/HMG-stimulated IVF cycles

The influence of the duration of the serum oestradiol (E2) rise before human chorionic gonadotrophin (HCG) injection on the outcome of in-vitro fertilization (IVF) cycles was investigated. Two different stimulation protocols were compared. In 218 cycles, the Norfolk protocol for stimulation with human menopausal gonadotrophin (HMG) was used (protocol A). In 235 cycles, pituitary function was suppressed by a single injection of a long-acting GnRH analogue ('Decapeptyl microcapsules') before HMG stimulation was started (protocol B). The overall pregnancy rates were significantly higher with protocol B (22% per puncture, 21% per started cycle) than with protocol A (14% per puncture, 9% per started cycle). For each interval of E2 rise duration (5-11 days), the fertilization rates (per oocyte) and the pregnancy rates (per puncture) were evaluated. There was a clear-cut maximum of the pregnancy rates for 6 and 7 days of E2 rise (21 and 16% respectively) for protocol A. For protocol B, pregnancy rates were generally higher than for protocol A. There was also a maximum of the pregnancy rates for 6 (32%) and 7 (29%) days of E2 rise but this maximum was not as clear-cut as for protocol A. The fertilization rates showed no significant differences for each interval of E2 rise in both groups (between 63 and 89%). Therefore, it is concluded that endometrial maturity, and not the oocyte's ability for fertilization, is the most critical factor for success in IVF cycles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrinology: High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome

This study was aimed at assessing the outcome of in-vitro fertilization(IVF) and embryo transfer in patients with polycystic ovariansyndrome (PCOS). The results of IVF and embryo transfer in PCOSpatients (PCOS group, 78 cycles of 26 patients) were comparedwith those of a control group (423 cycles in 202 patients withoutmale factor; age and ovarian stimulation protocol were matched).Although the pregnancy rate per transfer was not different inthe two groups of patients (25 versus 34%, PCOS versus controlgroup), the PCOS group had a significantly lower pregnancy rateper follicle aspiration (19 versus 31%, P < 0.05). A notableresult was a significantly higher incidence of embryo transfercancellations in the PCOS group (22 versus 8%, P < 0.01),which resulted from unpredictable failure of either oocyte recoveryor fertilization. The incidence of unexplained complete failureof fertilization was significantly higher in the PCOS group(18 versus 5%, P < 0.01). These results may reflect a reducedquality of the oocytes in the PCOS group, and there was a subgroupof PCOS patients who repeatedly produced poor results of treatment.Although the ovarian stimulation regimen best suited to PCOSpatients remains to be determined, special care should be takenduring ovarian stimulation, especially when the PCOS patientshad experienced unexplained failure of oocyte recovery or fertilizationin the previous treatment cycle(s).     

Ovarian stimulation for in-vitro fertilization

In-vitro fertilization (IVF) and embryo transfer has becomean accepted clinical method for the treatment of sterility.Different types of ovarian stimulation have been used successfully.The therapeutic principles behind the stimulation treatmentin an IVF programme are the same as those applied in the treatmentof normal and hypogonadotrophic ovarian insufficiency. Theseinclude clomiphene therapy with sub sequent HCG administration,combined clomiphene/HMG administration and stimulation withHMG alone, followed by HCG. A new approach to the stimulationof follicular development and oocyte maturation is the use ofpure FSH and GnRH analogues. The principal indications, results,advantages and disadvantages of these different schemes of ovarianstimulation for oocyte retrieval are discussed.     

Time of insemination and its effect on in-vitro fertilization, cleavage and pregnancy rates in GnRH agonist/HMG-stimulated cycles

In this prospective study, we compared the effect of delayed inseminations on fertilization, cleavage and pregnancy rates in two groups of patients. In one group, the ovarian stimulation was performed with a clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin (CC/HMG/HCG) protocol. The other group was pre-treated with gonadotrophin-releasing hormone agonist (GnRHa) and ovarian stimulation was carried out with an HMG/HCG protocol. Under both protocols, a delay of 2, 4 or 6 h in insemination showed no significant differences in the fertilization, cleavage or pregnancy rates. To find out which type of oocyte has the potential for better fertilization, cleavage and implantation, a simple oocyte classification scheme is proposed. In the GnRHa/HMG group, 9% post-mature, 90% mature and only 1% immature oocytes were retrieved. The post-mature oocytes showed a tendency towards reduced fertilization when insemination was delayed. The mature and slightly immature oocytes fertilized equally well when spermatozoa were added 2, 4 or 6 h after retrieval. Similarly, no significant difference was observed in the cleavage (80%) or fragmentation (20%) rates of these oocytes. The pregnancy rates after inseminations delayed for 2, 4 and 6 h were 14, 27 and 26%, respectively. Though these figures were not statistically significant, the 4- and 6-h groups in both the IVF and zygote intra-Fallopian transfer treatments showed a slightly improved pregnancy rate compared to the 2-h group. An insemination delay of 4 h is advocated on a routine basis.     

Increased pregnancy failure rates after clomiphene following assisted reproductive technology.

The obstetric outcome of 1941 in-vitro fertilization (IVF) and 1436 gamete intra-Fallopian transfer (GIFT) pregnancies reported from 25 units in Australia and New Zealand have been reviewed. Recently, gonadotrophin-releasing hormone analogues (GnRHa) have replaced clomiphene as part of many ovarian stimulation protocols. Clinical abortion rates after clomiphene (24.4% for IVF; 23.0% for GIFT) were not significantly higher than after GnRHa (20.7% for IVF; 17.9% for GIFT) when IVF and GIFT data were considered separately. However, the abortion rate for combined IVF and GIFT was significantly higher after clomiphene than after GnRHa. This pattern was found for most maternal age groups and causes of infertility although differences were not significant in all categories. The combined IVF and GIFT ectopic pregnancy rate of 6.7% for clomiphene was significantly higher than 4.1% for GnRHa. Because the mechanism of action of clomiphene for oocyte recruitment during folliculogenesis means that GnRHa cannot be used with clomiphene, luteinizing hormone (LH) levels are higher in clomiphene cycles than in GnRHa cycles. Clomiphene itself could cause the increase in pregnancy wastage or increased levels of LH during follicule genesis associated with the use of clomiphene may cause the observed pregnancy failures.