The "vanishing embryo" phenomenon in an oocyte donation programme

BACKGROUND: We studied the incidence of vanishing embryos (VE) in pregnancies achieved by oocyte donation and evaluated the obstetric and perinatal complications. METHOD: A retrospective study was carried out based on a chart review of 399 patients with multiple pregnancies from our oocyte donation programme. We defined vanishing phenomenon as the early resorption, in the first trimester, of one or more embryos in a multiple gestation, after confirming embryonic heart activity by transvaginal ultrasound. RESULTS: Vanishing embryo was observed in 75 patients (18.8%). In 60 patients (80%) this phenomenon occurred before the ninth gestational week. A higher incidence of VE was observed in patients who initially showed a higher number of gestational sacs (P < 0.03). Vaginal bleeding in the first trimester was significantly higher in patients with VE (P < 0.005). Miscarriage rate was similar in pregnancies with and without VE (P = NS). The incidence of pregnancy induced hypertension was decreased in the group with VE (P < 0.03). Preterm spontaneous rupture of membranes occurred more frequently in pregnancies with VE (P < 0.05). However, gestational age at delivery was similar in the group with VE and the controls. CONCLUSIONS: The high incidence of VE in pregnancies achieved by oocyte donation should be considered when counselling patients with high order multiple gestations.     

Semen donor recruitment in an oocyte donation programme

The article presents a new system for the recruitment of gamete donors. The system is a partial application of the mirror exchange system: the male partner of a couple donates sperm, and in return, he receives the guarantee that his partner benefits from a greatly reduced waiting time for donor oocytes. More specifically, the woman will obtain donor oocytes within a period of 8 months. The procedure was very successful in recruiting sperm donors while avoiding the ethical objections raised against other incentives to attract donors. The data indicate that the system would also work to encourage IVF patients to share their oocytes.     

Implantation: Uterine receptivity in an oocyte donation programme

Oocyte donation is a useful model for the assessment of potentialfactors affecting implantation since embryos generated are fromyounger oocytes than in in-vitro fertilization programmes andare therefore expected to have higher and more consistent implantationrates. Transvaginal sonographic measurement of endometrial thickness,echogenic pattern and uterine artery impedance, measured aspulsatility index (PI) and resistance index (RI), were retrospectivelycompared in 99 recipient women following 117 fresh embryo transfersthat resulted in 51 conception cycles and 66 non-conceptioncycles. The prevalence of a multilayered echogenic pattern wassignificantly greater (91.2%) in conception than in non-conception(44.4%) cycles. No differences in endometrial thickness, PIor RI were observed between conception and non-conception cycles.However, no pregnancy occurred when the PI was 3.4 (sensitivity100%). The number of days or cumulative dose of oestrogen intakeand the serum oestradiol concentration prior to progesteroneadministration were not different in the multilayered patternversus other echogenic pattern groups. The data show that itmay be beneficial to await achievement of a PI < 3.4 anda multilayered pattern endometrium prior to embryo transferin an oocyte donation programme.     

Supraphysiological estradiol levels do not affect oocyte and embryo quality in oocyte donation cycles.

BACKGROUND: The study aim was to determine whether supraphysiological estradiol (E(2)) levels reduce oocyte/embryo quality in oocyte donation cycles. METHODS: A retrospective analysis of 330 consecutive fresh oocyte donation cycles was performed in an assisted reproductive treatment programme between January 1996 and December 2000. Throughout the study period, oocyte donors and recipients followed a standard synchronization regimen that did not vary. A serum E(2) level (peak E(2)) was obtained from all oocyte donors on the morning of HCG administration. Peak E(2) values were grouped by 33rd percentile (group I, <1500 pg/ml; group II, 1500-3000 pg/ml; and group III, >3000 pg/ml). All embryo transfers were performed on day 3 after oocyte recovery. RESULTS: Comparisons between groups revealed no significant differences in the quality of oocytes retrieved, and in fertilization rates. Higher peak E(2) levels were directly correlated with a greater number of oocytes retrieved, embryos available for transfer and cryopreservation, and higher average embryo quality scores (P < 0.005). Compared with group I, group III had significantly higher embryo implantation rates (P < 0.05). CONCLUSIONS: Sustained supraphysiological E(2) levels do not adversely affect the quality of developing oocytes and embryos. On the contrary, elevated E(2) levels are associated with a larger number of oocytes and embryos and high-grade embryos for transfer/cryopreservation and, consequently, improved implantation rates.     

Combined treatment by pentoxifylline and tocopherol for recipient women with a thin endometrium enrolled in an oocyte donation programme

BACKGROUND: To evaluate the effect of an antifibrotic treatment by a combination of pentoxifylline (PTX) and tocopherol (vitamin E) in patients with a thin endometrium who were enrolled in an oocyte donation programme. METHODS: Eighteen oocyte recipients who failed to develop a pre-ovulatory endometrial thickness of at least 6 mm after receiving vaginal micronized estradiol were enrolled in the study. The patients received a combination of PTX (800 mg/day) and vitamin E (1000 IU/day) for 6 months. The main outcome measurements were the change in endometrial thickness and the pregnancy and delivery rates after treatment. RESULTS: Endometrial thickness increased significantly (P <0.001), with a mean of (+/-SD) 4.9 +/-0.6 mm before and 6.2 +/- 1.4 mm after treatment, with 72% (13/18) of patients being good responders. Five patients either did not respond to the treatment or responded only slightly. Three patients, of which two had received previous radiotherapy, became spontaneously pregnant, and two became pregnant after embryo transfer. Three patients did not have embryo transfer. A total of four babies were delivered. The pregnancy rate was thus 33% and the delivery rate 27%. CONCLUSION: Treatment by combination of PTX and vitamin E appears to improve the pregnancy rate in patients with a thin endometrium by increasing the endometrial thickness and improving ovarian function. This was especially noticeable in patients who had previously received total body irradiation.     

Comparative assessment of pre- and post-donation attitudes towards potential oocyte and embryo disposition and management among ovum donors in an oocyte donation programme

BACKGROUND: In anonymous oocyte donation programmes, the disposition of retrieved oocytes and subsequent embryo management are at the discretion of the IVF programme and the oocyte recipients, as donors waive all rights following their donation. Nonetheless, donors are routinely made aware of ways in which oocytes and resulting embryos may be used and elect to proceed with the process even in the presence of reservations to some clinical scenarios before their donation. The aim of our study was to examine oocyte donors' attitudes to oocyte and embryo disposition and management and how initial reservations change over the course of the donation process. METHODS: Oocyte donors in a university-based IVF programme were asked about their willingness to donate in relation to various clinical scenarios during the initial screening interview and at the post-donation exit interview. Results were tabulated as 'yes' or 'no'. RESULTS: At the pre-donation interview, 72% of donor candidates expressed reservations to one or more clinical scenarios. More reservations were expressed at the post-donation interview compared with the pre-donation interview. The greatest reservations were donating to recipients >50 years of age (P < 0.05). Despite this, 97% of donors were willing to donate again. CONCLUSION: Oocyte donors' attitudes towards various clinical scenarios changed following their donation, reflecting overall greater reservations following the donation process. Although speculative, donors may be more willing to assert their opinions or donor attitudes become more restrictive.     

Synchronization of donor's and recipient's cycles with GnRH analogues in an oocyte donation programme

In this oocyte donation programme nine female donors were stimulated using a combination of GnRH analogues and human menopausal gonadotrophins. A total of 149 oocytes were retrieved. Thirty fresh embryos were transferred in 14 uterine replacements, resulting in four pregnancies and 15 fertilized oocytes were placed in the Fallopian tube of six recipients, yielding two pregnancies. A mean number of 2.2 embryos was replaced. The implantation rate per embryo was 13%. Furthermore 36 embryos were cryopreserved for later use. Following 20 replacements, six pregnancies were established (30% per transfer); since two patients aborted, the ongoing pregnancy rate was 20%.     

Twin pregnancy following embryo transfer on day 7 of the luteal phase in an oocyte donation programme

We report a case of a 42 year old female patient with hypergonadotrophichypogonadism requiring oocyte donation. Spontaneous ovulationoccurred during a hormonal replacement treatment cycle and threeembryos were transferred 7 days after documented ovulation.This resulted in a viable twin pregnancy. The twins were geneticallydistinct from the mother. To the best of our knowledge thisis the first reported case of a successful transfer of embryoson day 7 of the luteal phase leading to a viable pregnancy inan oocyte donation programme.     

Immunology: Repeat trials of oocyte donation to women with previous donor oocyte success

Oocyte donation has proven to be highly successful in establishingpregnancy in functionally agonadal women. Both implantationand ongoing pregnancy rates in women using this method havesurpassed those normally seen in standard in-vitro fertilization(IVF) patients. Over a 5 year period, seven women who had previouslyconceived using oocyte donation elected to attempt pregnancyand deliver a second child using the same donor. In each casethe paramount consideration was to provide a sibling of thesame genetic make-up as the child or children previously borne.Of the seven women studied, whose ages ranged from 24 to 44years, five became pregnant on subsequent cycles. The time toconception varied from one to a maximum of three attempts withthree of the five women becoming pregnant on the first cycleand two requiring three cycles to establish the subsequent pregnancy.The overall rate of success in this group was 12 pregnanciesin 20 cycles of embryo transfer (60%). An exaggerated implantationrate (25.6%) was also noted (23 individual embryo implantationsfrom 90 embryos transferred). Of the 12 pregnancies establishedin these seven women, four (33%) were multiple gestations (threetriplets, one twin). We conclude that women who have previouslyexperienced pregnancy following oocyte donation are highly likelyto conceive in a subsequent trial at a rate that may be higherthan that normally seen in the general population of women undergoingoocyte donation.     

A flexible protocol for the induction of recipient endometrial cycles in an oocyte donation programme

Synchronization of the availability of good quality oocytesfrom donors and adequate endometrial maturation of recipientsare very important for the success of an oocyte donation programme.A flexible protocol for the endometrial preparation of recipientsis important in timing embryo transfer between days 17 and 19of the cycle (‘window of receptivity’). The purposeof this study was to evaluate the effect of the length of oestradioladministration to recipients on pregnancy outcome. Oestrogenadministration was 8 mg/day, but its length varied prospectivelyfrom 6 to 27 days, followed by the addition of progesterone(100 mg daily Lm.) for 2–4 days according to the availabilityof good quality oocytes. Pregnancy outcome was evaluated regardlessof age, indication for oocyte donation or number of embryostransferred per patient The pregnancy rate per cycle was comparablewhen oestradiol was administered from 6 to 11 days before progesteroneaddition, while it dropped significantly thereafter. The variationin progesterone administration did not affect pregnancy outcome.These findings provide us with a greater flexibility by allowingus to vary oestradiol administration to recipients from 6 to11 days prior to progesterone, reducing considerably, therefore,the need to cancel embryo transfer because of oocyte unavailability.Thus we can arrange to transfer embryos between days 17 and19 of the recipient's cycle so as to obtain the best possibleclinical outcome.     

Elective single embryo transfer yields good delivery rates in oocyte donation

BACKGROUND: High pregnancy rates have been noted after oocyte donation (OD). Multiple pregnancies should be avoided, because oocyte recipients have an increased risk of obstetric complications. METHODS: We analysed our OD results from 2000-2001 when elective single embryo transfer (eSET) was introduced as a recommended policy for all recipients if at least one good quality embryo was available. The results were compared with those achieved in 1998-1999, when usually two embryos were transferred (double embryo transfer, DET). Between 1998 and 2001, 100 healthy women donated oocytes and 135 fresh embryo transfers were carried out. The mean age of the donors was 31 years and that of the recipient women was 35 years. RESULTS: The proportion of eSET of all OD transfers was 17.1% in 1998-1999 and 61.0% in 2000-2001. There was no statistically significant difference in clinical pregnancy (36.8 versus 45.8%) and delivery rates (31.6 versus 33.9%) per embryo transfer between the two time periods. The proportion of twins declined from 29% (1998-1999) to 10% (2000-2001). The delivery rate was similar after eSET and DET (32.6 versus 32.1% respectively). CONCLUSIONS: By increasing the proportion of eSETs it is possible to reduce the number of twins without affecting delivery rates in oocyte recipients.     

Long oestradiol replacement in an oocyte donation programme

The objective of this study was to optimize, in terms of endometrialreceptivity (embryo implantation), the limits of unopposed administrationof oestrogens beyond 35 days in an in-vitro fertilization (IVF)and ovum donation programme. Oocytes donated by 182 women undergoingIVF were distributed among 186 women treated by ovum donation.Five groups of recipients were established according to theduration of oestradiol valerate administration, in a ‘prolongedfollicular phase’ protocol, before embryo replacement,employing oestradiol valerate at increasing doses up to 6 mg/day.Gonadotrophin-releasing hormone analogues (GnRHa) were simultaneouslyadministered in ovulatory patients. The dosage of oestradiolvalerate was maintained until oocytes were available for inseminationand subsequent transfer. Donors and recipients were equallydistributed among groups in terms of age and cause of infertility.There was no difference among groups in serum oestradiol concentrationthe day in which progesterone was added to obtain a secretorytransformation of the endometrium. An analysis of the ovum donationcycles showed no difference among groups in pregnancy and implantationrates after the replacement of a similar number of embryos.Successful implantation was observed even after 100 days ofunopposed oestradiol valerate administration. Break-throughbleeding increasingly appeared according to the duration ofoestrogen replacement. These clinical observations provide evidencethat the concept of ‘prolonged follicular phase’oestrogen replacement for ovum donation can be maintained, atleast as long as 15 weeks. However, because of the high (>44%)incidence of break-through bleeding after 9 weeks, it is advisableto stop oestrogen treatment at this point. This protocol enormouslyfacilitates the chances of synchronization between donor andrecipient in an anonymous oocyte donation programme.     

The births of five Spanish babies from cryopreserved donated oocytes

BACKGROUND: The technique of freezing oocytes is still not widely used. Reasons cited for this include the technique's low efficacy and the risk of aneuploidy. However, the introduction of technical changes (the type and concentration of cryoprotective substances; slow freezing and rapid thawing; and fertilization by ICSI) has led to improved results. We present four pregnancies obtained using mature oocytes (in metaphase II) that had been frozen and thawed. The oocytes were donated by young women who were not patients. METHODS: The frozen oocytes (n = 88) came from seven donors aged 18-25 years. The metaphase II oocytes, morphologically normal in appearance, were denuded of their cumulus-corona complex. The cryoprotective freezing solution contained 1,2-propanediol (1.5 mol/l) and sucrose (0.3 mol/l). Freezing was slow and thawing rapid. The oocytes were fertilized by ICSI. RESULTS: Seventy-nine of the 88 thawed oocytes survived (89.8%); 58 were fertilized (73.4% of all those microinjected); and 26 were transferred (44.8% of all those fertilized). Four pregnancies were produced after seven transfers (57.1%). Five children were born from four pregnancies. CONCLUSIONS: With the freezing/thawing technique used, oocyte survival was high ( approximately 90%). The pregnancy rate with frozen oocytes was similar to that obtained using fresh oocytes from donors ( approximately 50%).     

Oocyte and embryo quality after coasting: the experience from oocyte donation

BACKGROUND: Oocyte donation provides us with an opportunity to study the clinical outcome of oocytes, retrieved from women undergoing coasting, in recipients in whom endometrial receptivity is unaltered by the coasting procedure. Thus, our aim was to describe oocyte donation outcome in donors undergoing coasting, the oocyte and embryo quality obtained from these cycles, and to determine the influence of coasting duration in the cycle outcome. METHODS: Matched-paired analysis included 15 oocyte donors with high response to ovarian stimulation and submitted to coasting and 15 oocyte donors with normal response to ovarian stimulation and not undergoing coasting. There were 38 oocyte recipients who shared oocytes from the donors under coasting and 37 from donors not undergoing coasting. RESULTS: Both groups of donors were comparable in terms of days and dose of ovarian stimulation, oocytes retrieved, metaphase II oocytes obtained, and in the appearance of ovarian hyperstimulation syndrome. Both groups of oocyte recipients were comparable in male-associated factor, pregnancy and implantation rates, as well as in embryo quality. Recipients from donors with coasting for >4 days had significantly lower implantation and pregnancy rates. CONCLUSIONS: the outcome of oocyte donation from donors undergoing coasting is not impaired, as good implantation and pregnancy rates are achieved. Embryo quality, according to our current standards, does not seem to be compromised by coasting itself. However, if coasting in oocyte donors is prolonged for >4 days there is a significant decrease in both implantation and pregnancy rates.     

Stringent regulation of oocyte donation in China

Currently in China, health regulations permit oocyte donationonly from IVF/ICSI patients who have 20 or more mature oocytesretrieved from a single cycle, of which at least 15 must bekept for their own treatment. Oocyte donation from non-patientsand commercial transaction of human gametes are strictly prohibitedby law. Additionally, embryos derived from donated oocytes mustbe cryopreserved and cannot be transferred to prospective recipients,until donors have been screened to be free of communicable diseasesafter 6 months. Such overly stringent regulation has in turnled to a severe shortage of available donor oocytes in China.The situation is made worse by a cultural aversion to oocytedonation by the majority of patients, because biological kinshipand blood relations are viewed as sacrosanct in traditionalChinese culture. The harsh social stigmatization of childlessnessin Chinese society, increasing incidence of age-related femaleinfertility in recent years and growing numbers of bereavedolder women who have lost their only child to accidents, naturaldisasters and suicides would make it imperative to reconsiderliberalizing the regulation of oocyte donation in China. Inparticular, the blanket ban on oocyte donation by non-patientsshould be lifted, as it is anticipated that there are many younghealthy women in China who are generous and open-minded enoughto consider altruistically donating their oocytes to childlesscouples.     

Pregnancies after oocyte donation in women with ovarian failure caused by an inactivating mutation in the follicle stimulating hormone receptor.

BACKGROUND: An inactivating point mutation (Ala189Val) in the FSH receptor (FSHR) causes primary ovarian failure. It has not been known if FSH action is necessary during pregnancy and childbirth. METHODS: In 1991-2001, donated oocytes were used to treat the infertility of 12 women with ovarian failure due to this mutation. RESULTS: When 30 fresh and 15 frozen-thawed embryo transfers were performed, 14 clinical and two biochemical pregnancies resulted. To date, 12 children have been born to eight women, while one pregnancy ended in miscarriage. Three women had twin pregnancies, and one woman has delivered twice. Additionally, there are three ongoing pregnancies, of which two are second pregnancies of women who previously had a normal delivery after similar treatment. In all, 10 out of the 12 women became pregnant. Two deliveries were by Caesarean section. The rate of complications was comparable with that in pregnancies resulting from oocyte donation in general. CONCLUSIONS: Achieving and undergoing a successful pregnancy is possible when FSH action is severely decreased. Oocyte donation is an effective infertility treatment for women with FSHR mutations.     

The role of oocyte donation in women who are unsuccessful with in-vitro fertilization treatment.

Oocyte donation improves the chances of becoming pregnant in some women who are unsuccessful with in-vitro fertilization (IVF) treatment. A total of 119 IVF cycles achieved a pregnancy rate per cycle of 2.5% whereas the same women, when treated with 45 cycles of oocyte donation, achieved a 24.5% pregnancy rate per cycle. To ascertain which women may be helped by oocyte donation, IVF data were analysed according to the outcome of oocyte donation. There was a difference in the number of previous natural conceptions and live births, and in the IVF fertilization rate. There was no difference in the age of the women and the numbers of oocytes collected per cycle of IVF. New criteria are therefore suggested for recommending oocyte donation to women who have previously failed to become pregnant with IVF treatment.     

The effect of propofol anaesthesia on oocyte fertilization and early embryo quality

Propofol, frequently used for i.v. induction of anaesthesia in assisted reproduction procedures, has been suspected of damaging oocytes. Concentrations of propofol have recently been shown to increase in follicular fluid during oocyte retrieval. Our study was designed to assess whether exposure to increasing concentrations of propofol has a measurable effect on in-vitro fertilization, cleavage and embryo development. A cohort of 130 women underwent i.v. anaesthesia using propofol and fentanyl. Time of anaesthesia from i. v. injection of propofol was measured, as were the doses of the two drugs. In 32 women expected to have more than 15 oocytes retrieved, first, middle and last oocytes were cultured separately. The mean time from i.v. injection to first follicle aspiration was 200 s. The mean time for the aspiration of each additional oocyte was 17.6 s. In 10 out of 11 cases where follicular fluid concentrations of propofol were measured, there was an increase from the first to the last follicle, but no difference was found in the ratio of mature to immature oocytes. Nor were any differences found in fertilization, cleavage and embryo cell number. In so far as in-vitro development reflects embryo quality, we conclude that the time elapsed between retrieval of the first and last oocyte does not affect oocyte quality.     

A follow-up study of women who donated oocytes to known recipient couples for altruistic reasons

BACKGROUND: Current legislation in Canada allows for only altruistic gamete donation. Limited clinical data are available on the emotional and psychological impact of altruistic oocyte donation on known donors. METHODS: Seventeen women who had donated oocytes to known parties without financial compensation agreed to receive the oocyte donation questionnaire (ODQ) to explore the psychological domains of altruistic oocyte donation. RESULTS: Thirteen ODQ were returned, giving a response rate of 76%. All subjects indicated that they were primarily motivated by a 'desire to give and help' the recipient couple. Most subjects did not find the donation decision difficult but some found the post-donation psychological adjustments challenging. Subjects also indicated that mandatory counselling on the psychological implications of oocyte donation was an important component of cycle preparation. The majority of subjects had disclosed the donation to others and felt that disclosure to the presumptive child was essential. CONCLUSIONS: The findings provide clinical materials for conceptualizing the dynamics entailed by known altruistic oocyte donation, with regards to motivation, relationship implications, donor satisfaction and plans for disclosure. The data support the provision of psycho-social support services to help donors dealing with any residual emotional difficulties regardless of the outcome of oocyte donation.     

Counselling couples and donors for oocyte donation: the decision to use either known or anonymous oocytes

In order to avoid a long waiting period, the Centre for Reproductive Medicine of the Free University of Brussels suggests that couples in need of donor oocytes search for a donor among family and friends. Recipient couples can choose between two types of donation: known donation, i.e. treatment with the oocytes of the donor recruited by the couple, or anonymous donation, i.e. an exchange of the donor recruited by the couple with a donor recruited by another couple in order to ensure anonymity between donor and recipients. In total, 144 couples were counselled by a psychologist in the decision-making process with regard to the kind of donation to be used. Some 68.8% of the recipient couples preferred known donation. This choice was mainly motivated by reasons related to fears associated with anonymity, such as fear of the unknown origin of genetic material and the trust that couples had in 'their' donor. Almost one-third of the couples opted to use anonymous oocytes. The desire to establish explicit boundaries between the two families involved was the major motivation for this choice. Approximately 44% of the couples were willing to tell the child about the oocyte donation.