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.     

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.     

Endocrinology: Pure and highly purified follicle-stimulating hormone alone or in combination with human menopausal gonadotrophin for ovarian stimulation after pituitary suppression in in-vitro fertilization

The use of pure follicle stimulating hormone (pFSH) and highlypurified FSH (FSH-HP) versus the combinations pFSH/human menopausalgonadotrophin (HMG) and FSH-HP/HMG, respectively, was comparedfor stimulating follicular development after gonadotrophin-releasinghormone agonist (GnRHa) suppression in women undergoing in-vitrofertilization (TVF)—embryo transfer. Two consecutive prospective,randomized studies were carried out at the Assisted ReproductionUnit of the Hospital Clínic i Provincial in Barcelona,a tertiary care setting. Two groups of 188 (study 1) and 252(study 2) consecutive infertile patients respectively, scheduledfor IVF-embryo transfer were included. Pretreatment with leuprolideacetate (long protocol) was followed by gonadotrophin treatmentin all patients. In study 1, 92 patients received i.m. pFSHalone (group pFSH) and 96 were treated with the combinationof i.m. pFSH and i.m. HMG (group HMG-1). In study 2, 123 patientsreceived s.c. FSH-HP alone (group FSH-HP) and 129 patients weregiven the combination of s.c FSH-HP and i.m. HMG (group HMG-2).Main outcome measures included follicular development, oocyteretrieval, fertilized oocytes, duration and dose of gonadotrophintherapy, and clinical pregnancy. There were no significant differencesbetween pFSH and pFSH/HMG nor between FSH-HP and FSH-HP/HMGcycles with regard to the number of ampoules of medication used,day of human chorionic gonadotrophin (HCG) administration, meanpeak serum oestradiol concentrations, number of follicles punctured,and number of oocytes aspirated, embryos transferred, or pregnancies.We conclude that urinary FSH (either purified of highly purified)alone is as effective as the conventional combination of urinaryFSH/HMG for ovarian stimulation under pituitary suppressionin IVF cycles. Therefore, they can be used interchangeably inFVF programmes.     

Endocrinology: A comparison of two starting doses of human menopausal gonadotrophin for follicle stimulation in unselected patients for in-vitro fertilization

Ovarian responses and embryology data were compared in patientsundergoing in-vitro fertilization following follicular stimulationusing long course gonadotrophin-releasing hormone (GnRH) analogue/humanmenopausal gonadotrophin (HMG) in which the initial daily dosewas two (150 IU) or three ampoules (225 IU) maintained for aminimum of 7 days. Group 1 (n = 31; centre A) patients weretreated with a starting dose of two ampoules, while group 2(n = 46; centre A) patients were treated chronologically immediatelybefore group 1 with a starting dose of three ampoules per day.Group 3 (n = 74; centre B) patients were treated with threeampoules per day simultaneously with group 1. There was no differencein the distributions of patient ages or reasons for treatmentbetween the three groups. Group 1 required longer treatmentbefore the plasma oestradiol attained 250 pg/ml than did boththe other groups (group 1, 9.0; group 2, 6.9; group 3, 6.7 days;P < 0.01), and this resulted in a longer follicular phasefor group 1 (mean: 14.5 days compared with 12.7 and 12.8 forgroups 2 and 3 respectively; P < 0.05). The numbers of follicles>16 mm in diameter at human chorionic gonadotrophin (HCG)administration and the numbers of eggs and embryos were allsignificantly lower (P < 0.04) in group 1, and cycle cancellationsdue to insufficient ovarian responses were higher (P < 0.02)in group 1. There was no difference in the numbers of ampoulesused, the oestradiol concentration at HCG, the fertilizationand pregnancy rates or the incidence of hyperstimulation syndromein the three groups. The lower starting dose, therefore, yieldedinferior responses without significant reduction in the HMGrequirement.     

Short-term use of buserelin in combination with human menopausal gonadotrophins for ovarian stimulation for in-vitro fertilization in endocrinologically normal women

Ten endocrinologically normal women were injected subcutaneously with 500 micrograms D-Ser(TBU)6-EA10-LHRH (buserelin) on days 3,4 and 5 after the start of the menses. Two types of response were observed. Five women (group A) responded promptly and had a mean number of 13.4 oocytes retreived after 11.4 days of stimulation. In the second group (B), two to three times more HMG was needed to obtain a mean number of 7.3 oocytes after 17.2 days of stimulation. The response upon stimulation could be predicted by the serum gonadotrophin output on days 4 and 5 of the cycle. One woman from group B had a premature LH rise on day 16 and luteinization; her cycle was abandoned. In the four other patients of group B, serum and urinary LH concentrations showed that pituitary gonadotrophin secretion had recovered before the ovulatory stimulus, without signs of premature luteinization. Two women in each group became pregnant, one of whom aborted. This short-term GnRH agonist treatment could be an alternative method for ovarian stimulation, although it did not totally prevent the occurrence of an endogenous LH surge.     

Conversion of cycles involving ovarian hyperstimulation with intra-uterine insemination to in-vitro fertilization

Conversion to in-vitro fertilization (IVF) and embryo transferas an alternative to cancellation was offered in 27 consecutivecycles of controlled ovarian hyperstimulation and intra-uterineinsemination (IUI) cycles with excessive follicular developmentin patients with idiopathic infertility. IVF and embryo transferwas performed in 25 cycles, resulting in 13 pregnancies (52%),with 22% of couples having at least two embryos cryopreserved.The pregnancies have resulted in one singleton and two twinbirths, one spontaneous abortion, and nine ongoing pregnancies(including one triplet gestation). Four patients developed severeovarian hyperstimulation syndrome (OHSS) after IVF and embryotransfer, including two cases requiring paracentesis. Threeof four OHSS patients were pregnant, resulting in live birthsof healthy twins, one spontaneous abortion and one ongoing singletongestation. In two cycles a spontaneous luteinizing hormone (LH)surge occured, preventing oocyte retrieval. For these two women,drainage of all follicles except the five most likely to fertilize(18–22 mm diameter) was performed, followed by IUI, withno pregnancies or OHSS observed. Conversion of patients fromIUI cycles to IVF/embryo transfer cycles avoids cancellationof the very cycles with the best chance of achieving pregnancy.OHSS remains a problem, necessitating extensive pre-IVF counsellingand post-transfer vigilance.     

Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis

In-vitro fertilization (IVF) is an effective infertility treatment for women with endometriosis, but most women need to undergo several cycles of treatment to become pregnant. This case-control study was designed to assess how consistently women with ovarian endometriosis respond to ovarian stimulation in consecutive treatment cycles compared to women with tubal infertility. We compared outcome measures in 40 women with a history of surgically confirmed ovarian endometriosis and 80 women with tubal infertility, all of whom had at least three IVF treatment cycles. The groups were matched for age and early follicular follicle stimulating hormone (FSH) concentration at their first IVF cycle. Outcome measures included number of follicles, number of oocytes, peak oestradiol concentration and number of FSH ampoules required per follicle. Cumulative pregnancy and live birth rates were calculated in both groups. The ovarian endometriosis group had a significantly poorer ovarian response and required significantly more ampoules of FSH per cycle, a difference that became greater with each subsequent cycle. However, cumulative pregnancy (63.3 versus 62.6% by fifth cycle) and live birth (46.8 versus 50.9% by fifth cycle) rates were similar in both groups. In conclusion, despite decreased ovarian response to FSH, ovarian endometriosis does not decrease the chances of successful IVF treatment.     

Establishing pregnancies after follicular stimulation for IVF with clomiphene citrate and human menopausal gonadotrophin only

Data are presented on establishing pregnancies by IVF during 1987 using only clomiphene citrate and human menopausal gonadotrophin for follicular stimulation. Of the 562 patients undergoing follicular stimulation, 80% reached oocyte recovery and 70% had at least one conceptus replaced. Patients having one or more (up to a maximum of four) conceptuses replaced demonstrated a significant increase in the establishment of pregnancies from one to two (14-29%: P = 0.035) and from two to three conceptuses (29-42%: P = 0.037). There was a significant decline in pregnancies when four conceptuses were replaced compared with three (P = 0.004). The data were also analysed according to the cause of infertility, specifically tubal, endometriosis, unexplained infertility and male factors only. After the replacement of conceptuses, the incidence of implantation and abortion was not significantly different. The incidence of pregnancy declined significantly after 35 years (26%) compared with women under 31 years (43%; P = 0.043). Of 129 women having three conceptuses replaced, in those greater than 35 years (63 patients) 23 (37%) became pregnant whereas in those less than 31 years (65 patients), 34 (52%; P = 0.05) became pregnant. Twenty-two per cent of stimulated cycles resulted in an endogenous LH surge and the incidence of patients having three conceptuses replaced in this group was lower than those in the HCG group (P = 0.007). Fertilization per oocyte was also significantly reduced (P less than 0.001) in patients with an LH surge. In total, 2824 oocytes were recovered and 57% fertilized with 54% of patients having three conceptuses replaced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Luteal phase and clinical outcome after human menopausal gonadotrophin/gonadotrophin releasing hormone antagonist treatment for ovarian stimulation in in-vitro fertilization/intracytoplasmic sperm injection cycles.

The luteal phase hormonal profile and the clinical outcome of 69 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) after ovarian stimulation with human menopausal gonadotrophin (HMG) and the gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix were analysed. Twenty-four patients received Cetrorelix 0.5 mg (group I) while in 45 patients Cetrorelix 0.25 mg was administered (group II). Human chorionic gonadotrophin (HCG) was used as luteal support. Nine clinical pregnancies were obtained in group I (37.5%) and 12 in group II (26. 6%). These results were not significantly different. Serum progesterone and oestradiol concentrations did not differ between the two groups either in pregnant or non-pregnant patients. An expected decrease of the same hormones was observed 8 days after the pre-ovulatory HCG injection in non-pregnant women. With regard to serum luteinizing hormone concentrations, a decrease was observed 2 days after the pre-ovulatory HCG injection and was maintained at almost undetectable levels throughout the entire luteal phase in both conception and non-conception cycles of group I and group II. This study demonstrates that different doses of GnRH antagonist do not have any impact on the luteal phase of IVF/ICSI cycles when hormonal support is given.     

An improved use of buserelin in ovarian stimulation for in-vitro fertilization

In earlier IVF programmes, subcutaneous buserelin (Suprefact, Hoechst) was initially administered three times per day (200 micrograms x 3); then twice daily (300 micrograms x 2). We now suggest that a single administration of 600 micrograms daily may be equally effective. In a preliminary study, 20 patients were selected on the basis of tubal or idiopathic infertility and received 0.6 ml buserelin subcutaneously once a day, beginning on day 1 or 2 of the cycle. A sufficient pituitary desensitization was obtained on day 10 in 75% of patients and on day 16 for 100% and the ongoing pregnancy rate was 35% per treatment cycle. A randomized study comparing the effect of 600 micrograms of buserelin administered in one (n = 50) or two injections (n = 46), has been carried out and indicates that the results in terms of the ovarian suppression and pregnancy rates, were similar. Therefore, this protocol represents a simplification of the treatment with buserelin.     

Consecutive versus alternating cycles of ovarian stimulation using human menopausal gonadotrophin.

Ovarian stimulation is an effective treatment for patients with ovulatory dysfunction and unexplained infertility. An initial report has suggested that consecutive cycles of ovarian stimulation can be employed without causing a diminished response in the second cycle. However, this observation has neither been confirmed nor has a regimen of consecutive stimulation cycles been compared to one of alternating stimulation cycles. Accordingly, 44 consecutive and 54 alternating cycles of stimulation were evaluated in patients (n = 42) who were treated with human menopausal gonadotrophin (HMG) alone. Human chorionic gonadotrophin (HCG) 10,000 IU was administered i.m. when at least one follicle exceeded 16 mm in mean diameter, and this was followed by either intercourse or intrauterine insemination. Using each patient as her own control, we were unable to demonstrate any differences in mean HMG dose requirements, endocrine parameters or follicular development on the day of HCG administration, or ovulation rates in the second consecutive cycle compared to the second alternating cycle. Clinical pregnancies resulted significantly more often in a consecutive cycle (8/22) than in an alternating cycle (2/27, P = 0.029). We conclude that consecutive cycles of ovarian stimulation with HMG are not detrimental and may, in fact, result in increased cycle fecundity compared to alternating stimulation cycles.     

Infertility: Semi-programmed ovarian stimulation as the first choice in in-vitro fertilization programmes

The objective of this work was to evaluate the results obtainedwith a protocol of semi-programmed ovarian stimulation (low-dosecontraceptive pill + clomiphene citrate + human menopausal gonadotrophin+ dexamethasone) used as the first-choice method for in-vitrofertilization (IVF). A total of 207 punctures was performedfor oocyte collection from 168 patients (mean age 31.0 ±4.0 years); mean infertility duration was 5.81 ± 3.30years. The infertility factors indicating IVF for this populationwere as follows: tubo-peritoneal factor, 68%; pure or associatedmale factor, 9.2%; endometriosis, 11.1%; ovulatory factor, 4.3%;idiopathic factor, 11.6%; others, 2.4%. No oocyte was foundon aspiration in five procedures (2.4%), with the mean numberof oocytes collected per cycle being 5.87 ± 3.3 (range0–18). The cancellation rate per puncture was 5%. Themean embryo cleavage rate was 60.2 ± 36.8%, with transferof at least one embryo occurring in 82.6% of all punctures.The mean number of transferred embryos was 2.52 ± 1.60(range 1–5). The clinical pregnancy rates per startedcycle and per puncture were 22.4 (218 ovarian stimulation cycles)and 23.6% (a total of 49 clinical pregnancies, 36 single, ninetwins and four triplets) respectively. The clinical pregnancyrate per embryo transfer was 28.6%. The embryo implantationrate was 12.6%. The abortion rate was 16.3%. The index of deliveriesper puncture was 19.8%. There were no cases of moderate or severeovarian hyperstimulation syndrome. The favourable results obtained,in addition to the low operational costs, confirm the validityof the use of semi-programmed cycles as the first choice forpatients undergoing the IVF process.     

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.     

Ultrasound measurement of endometrial thickness on different ovarian stimulation regimens during in-vitro fertilization

Endometrial thickness was measured ultrasonographically in threegroups of patients undergoing in-vitro fertilization (IVF) onthree different ovulation induction regimens. The endometrialthickness was comparable on all three regimens and similar tothat observed in a group of spontaneously ovulating, normal,fertile controls. These patterns of endometrial thickness wereobserved despite significantly higher levels of serum oestradiol-17In all of the hyperstimulated cycles, suggesting that in thenormal cyde a maximum response in terms of endometrial developmentmay be achieved. In the three conception cycles endometrialthickness continued to increase throughout the luteal phase,whilst In non-conception cycles plateauing of thickness increaseoccurred in the mid-luteal phase and reduction in late lutealphase. Whether ultrasonographic evaluation of endometrium duringIVF stimulation cydes has any prognostic value regarding predictionof conception has yet to be detennined.     

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.     

Bilateral salpingectomy does not compromise ovarian stimulation in an in-vitro fertilization/embryo transfer programme

The question whether salpingectomy has a negative influenceon ovarian function and the outcome of pregnancy in an in-vitrofertilization (IVF) and embryo transfer treatment programmeis not yet answered. We performed a retrospective case-controlstudy to investigate the possible negative effect of salpingectomyon ovarian response to human menopausal gonadotrophins (HMG)during IVF and embryo transfer. The study group was composedof 26 patients with bilateral salpingectomy. In 67 cycles weanalysed different parameters of ovulation such as the numberof days of ovarian stimulation, numbers of ampoules of HMG,pre-ovulatory oestradiol concentrations and the numbers of oocytesretrieved. These parameters were compared to a control groupof 134 cycles in 134 women with healthy Fallopian tubes. Nodifferences were found. Implantation ratio, pregnancy rate andoutcome were the same in both groups. We conclude that bilateralsalpingectomy had no detrimental effect on ovarian performanceduring IVF and embryo transfer treatment nor on the outcome.     

Early or late monitoring of stimulation of ovulation for in-vitro fertilization? A methodological discussion of a randomized study

Two GnRH agonist long-stimulation protocols, in association with HMG, are compared on a random basis. Group A (n = 53) was monitored daily from the 6th day of stimulation, whereas monitoring in group B (n = 55) began on the 11th day of stimulation. There was no significant difference in the numbers of follicles which matured, the numbers of collected oocytes, the numbers of embryos obtained in vitro and the clinical pregnancy rate. But the power of such a study is very weak (6%). It would have been necessary to include greater than 1000 patients in each group to obtain a bioequivalence test. Such a study is unrealistic for a single centre and multicentric studies are very difficult to achieve because of practical difficulties. A pooled analysis is perhaps the methodological answer.     

Accumulation of human chorionic gonadotrophin in the serum of patients during in-vitro fertilization treatment cycles with Pergonal

We examined the possible contribution of human chorionic gonadotrophin(HCG) in Pergonal to the serum luteinizing hormone (LH)-likebioactivity in 10 patients (median age32 years, range 28–38)with tubal infertility who were undergoing in-vitro fertilization(IVF), together with 19 controls (median age30 years, range21–43). IVF patients were treated with clomiphene (50mg twice daily) over days 2–6 and Pergonal (150 IU i.m.)daily from day 5 until at least day 10. Serum LH was measuredby fluoro-immunometric assay (I-LH) and in-vitro Leydig cellbioassay (B-LH). Serum HCG was measured by fluoro-immunometricassay. The data were analysed by paired two-tailed t-test, followinglogarithmic transformation. From days 1–5, there was anincrease in serum B-LH (mean, 95% confidence intervals givenin parentheses) from 8.3 (6.8, 10.2) IU/1 to 11.7 (9.8, 13.9)IU/1 [P= 0.004], and in serum I-LH from 4.5 (3.7, 5.4) IU/1to 5.4 (4.6, 6.3) IU/1 [P= 0.002]. From days 5–8, therewas a rise in B-LH to 16.6 (12.6, 21.9) IU/1 [P= 0.023]. Therise in I-LH to 6.3 (5.1, 7.8) IU/1 [P= 0.081] failed to reachsignificance. Furthermore, serum HCG was <<0.75 IU/1 untilafter Pergonal was administered on day 5, then rose to a plateauon day 8 at 1.2(0.8, 1.6) IU/1. Serum HCG in the controls remained<<0.75 IU/1 throughout. We conclude there is a disproportionateincrease in serum B-LH compared to I-LH from days 5–8,corresponding with a rise in serum HCG and the commencementof treatment with Pergonal. The HCG in Pergonal may be contributingto an undesirable rise in serum LH-like bioactivity, which mightreduce the success rate of IVF.     

A randomized comparative study of highly purified follicle stimulating hormone and human menopausal gonadotrophin for ovarian hyperstimulation in an oocyte donation programme

A randomized comparative study of highly purified human follicle-stimulatinghormone (FSH-HP), administered s.c, and human menopausal gonadotrophin(HMG), administered i.m., was carried out in 41 volunteer oocytedonors. The response to ovarian hyperstimulation was similarin both groups. One cycle in both groups was cancelled. Thenumber of oocytes recovered was 16.0 ± 7.9 (mean ±SD) following stimulation with 32.8 ± 103 ampoules ofFSH-HP (n = 19) over 12.3 ± 1.7 days. Following stimulationwith 29.8 ± 10.6 ampoules of HMG over 11.5 ± 1.6days, the number of oocytes collected was 18.4 ± 12.7(n = 20). The oocyte recipients were allocated 9.2 ±3.6 oocytes in the FSH-HP group (n = 33) and 9.6 ± 4.6oocytes in the HMG group (n = 37). The fertilization rate (2PN/cell)was significantly higher in the HMG group (48%, 170/355) thanin the FSH-HP group (36%, 109/304) (P < 0.01). The numberof embryos transferred per recipient was 2.0 ± 0.4 inthe FSH-HP and 2.0 ± 03 in the HMG group. The pregnancyrate per embryo transfer was 25% in the FSH-HP (5/20) and 26%(8/31) in the HMG group. Fertile donors with body mass index£25 made up a poor responder group to s.c FSH-HP, possiblyindicating reduced absorption of the drug.     

Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial

BACKGROUND: To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens. METHODS: Infertile patients under 38 years of age were randomly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not disrupt secondary follicle recruitment, or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF, embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres. RESULTS: The study was terminated prematurely, after an unplanned interim analysis (which included 61% of the planned number of patients) found a lower embryo aneuploidy rate following mild stimulation. Compared with conventional stimulation, significantly fewer oocytes and embryos were obtained following mild stimulation (P < 0.01 and < 0.05, respectively). Consequently, both regimens generated on average a similar number (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors. CONCLUSIONS: Future ovarian stimulation strategies should avoid maximizing oocyte yield, but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology.