Clinically significant intra-day variability of serum progesterone levels during the final day of oocyte maturation: a prospective study with repeated measurements.

STUDY QUESTION: Is there significant variability in progesterone levels during the final day of oocyte maturation in women undergoing ovarian stimulation? SUMMARY ANSWER: Progesterone levels drop from the basal level up to 44% during the final day of oocyte maturation in women undergoing ovarian stimulation. WHAT IS KNOWN ALREADY: It has been suggested that elevated progesterone levels on the final day of ovarian stimulation may be related to poorer outcomes in in vitro fertilization fresh cycles due to a negative impact on the endometrium. However, despite conflicting results regarding the actual effect of progesterone on pregnancy rates and the lack of a well-established cut off, currently many IVF patients have their embryo transfer deferred when progesterone values surpass a threshold of 1.5 ng/ml on the day of ovulation triggering. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study conducted in 22 oocyte donors of a university-affiliated fertility centre between November 2017 and January 2018. We calculated the sample size to detect a difference of 15% between the first and last progesterone measurements with a 5% false-positive rate in a two-sided test with 80% statistical power and a 95% confidence interval (CI). PARTICIPANTS/MATERIALS, SETTING, METHODS: Progesterone circulating levels were evaluated at four different times during the final day of oocyte maturation (08:00, 12:00, 16:00 and 20:00) before ovulation triggering in healthy oocyte donors. A flexible antagonist protocol was used, and ovarian stimulation was achieved with recombinant follicle-stimulating hormone (FSH) in all cases. The pairwise percentage differences in progesterone levels for each patient were calculated. Univariate linear regression analysis was adopted in order to evaluate variables associated with progesterone levels on the first measurement. The intra-day variability of progesterone was analysed using mixed models. MAIN RESULTS AND THE ROLE OF CHANCE: Mean serum progesterone values at 08:00, 12:00, 16:00 and 20:00 were 1.75 ng/ml, 1.40 ng/ml, 1.06 ng/ml and 0.97 ng/ml. The progesterone difference between 08:00 and 20:00 was 0.77 (95% CI, 0.56-0.99), which is equivalent to a 44% decline in the mean progesterone values between the first (08:00) and the last determination (20:00; P < 0.001). Among those patients with basal (08:00) progesterone levels >1.5 ng/ml (n = 10), 70% (n = 7) showed levels reduced to <1.5 ng/ml on the last determination of the day (20:00). A mixed model analysis revealed that the progesterone reduction during the day was significantly associated with time and total recombinant FSH dose administered. LIMITATIONS, REASONS FOR CAUTION: Only young healthy oocyte donors stimulated with an antagonist protocol using recombinant FSH were included. Extrapolation to the general IVF population, with different stimulation protocols and gonadotropins, needs to be confirmed. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that a single progesterone determination on the final day of oocyte maturation is not reliable enough to make clinical decisions due to the enormous variation in progesterone during the day. Further studies are needed to better define the impact of the follicular progesterone rise on the endometrium of IVF cycles. STUDY FUNDING/COMPETING INTEREST(S): Funding was granted from Fundació Santiago Dexeus Font. N.P.P. received unrestricted grants and/or lectures fees from Roche Diagnostics, MSD, Merck, Ferring Pharmaceuticals, IBSA, Theramex and BESINS International, not associated with the current study. The remaining authors have no competing interests. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03366025.

Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates.

A retrospective cohort study was performed to examine whether, in artificial endometrial preparation for frozen embryo transfer (FET) cycles, progesterone (P) levels the day prior to embryo transfer of euploid embryos have an impact on pregnancy outcomes. In a private university clinic, 244 FETs between January 2016 and June 2017 were analyzed. Endometrial preparation was achieved with estradiol valerate and vaginal micronized progesterone. Serum P and estradiol levels the day prior to embryo transfer were measured. A multivariable analysis to assess the relationship between serum P level and pregnancy outcomes was performed, adjusted for confounding variables. Mean P value was 11.3 ± 5.1 ng/ml. Progesterone levels were split in quartiles: Q1: ≤ 8.06 ng/ml; Q2: 8.07-10.64 ng/ml; Q3: 10.65-13.13 ng/ml; Q4: > 13.13 ng/ml. Patients included in the lower P quartile had a significantly higher miscarriage rate and significantly lower live birth rate (LBR) compared to the higher ones. A low serum P level (≤ 10.64 ng/ml) one day before FET is associated with a lower pregnancy and LBR following FET of euploid embryos.

How does vitrification affect oocyte viability in oocyte donation cycles? A prospective study to compare outcomes achieved with fresh versus vitrified sibling oocytes.

STUDY QUESTION: How does vitrification affect oocyte viability? SUMMARY ANSWER: Vitrification does not affect oocyte viability in oocyte donation cycles. WHAT IS KNOWN ALREADY: Oocyte vitrification is performed routinely and successfully in IVF and oocyte donation programs. STUDY DESIGN, SIZE, DURATION: This is a prospective study performed between June 2009 and February 2012 to compare ongoing pregnancy rates and other indices of viability between fresh and vitrified oocytes. A total of 99 donations with more than 16 oocytes (MII) in which oocytes were allocated both to a synchronous recipient (fresh oocytes) and to an asynchronous recipient (vitrified oocytes) were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were consenting couples (donors and recipients) from the oocyte donation program. On the day of retrieval, the oocytes allocated to the synchronous recipient were inseminated and those allocated for banking were denuded of cumulus and vitrified. Vitrified oocytes were microinjected with spermatozoa 2 h after warming. Embryo transfer was performed on Day 2 of development in both groups, and the remaining embryos were cryopreserved on Day 3. Clinical pregnancy was defined by a positive fetal heartbeat at 6 weeks. MAIN RESULTS AND ROLE OF CHANCE: A total of 989 oocytes were warmed and 85.6% survived. No significant differences were observed between fresh and vitrified oocytes: fertilization rate (80.7 versus 78.2%), ongoing embryo rate (71.0 versus 68.2%) or good-quality embryo rate (54.1 versus 49.8%). The mean number of embryos transferred was similar in both groups (1.82 ± 0.44 versus 1.90 ± 0.34). The implantation rate (33.3 versus 34.0%) and the multiple pregnancy rate (27.7 versus 20.8) were also similar between both groups (P > 0.05). The live birth rate per cycle was 38.4% in the recipients of fresh oocytes and 43.4% in the recipients of vitrified oocytes (P > 0.05). Eighty five frozen embryo transfers were also evaluated. Comparing embryos from fresh and vitrified oocytes there were no significant differences in the embryo survival rate (70.1 versus 65.8%), clinical pregnancy rate (40.8 versus 33.3%) or implantation rate (21.8 versus 26.8%). LIMITATIONS, REASONS FOR CAUTION: The oocytes were donated by healthy, young women (≤35 years) and these results cannot be extrapolated to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Outcomes obtained with vitrified oocytes are as good as with fresh oocytes and the use of vitrification can be extended to new applications, e.g. accumulation of oocytes from successive stimulations for preimplantation genetic diagnosis, for patients at risk of ovarian hyperstimulation syndrome or in patients needing to preserve their fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was done under the auspices of the Càtedra d'Investigació en Obstetrícia i Ginecologia of the Universitat Autònoma de Barcelona.

Assessment of progesterone levels on the day of pregnancy test determination: A novel concept toward individualized luteal phase support.

Research question: The main objective of the study is to define the optimal trade-off progesterone (P4) values on the day of embryo transfer (ET), to identify low P4-human chorionic gonadotropin (hCG), and to establish whether P4 supplementation started on the hCG day can increase the success rate of the frozen embryo transfer (FET) cycle. Design: A single-center, cohort, retrospective study with 664 hormone replacement therapy (HRT)-FET cycles analyzed female patients who received vaginal 600 mg/day of P4 starting from 6 days before the FET, had normal P4 values on the day before ET, and whose P4 on the day of the pregnancy test was assessed. Results: Of the 664 cycles, 69.6% of cycles showed P4 ≥ 10.6 ng/ml, while 30.4% showed P4 < 10.6 ng/ml on the day of the hCG. Of the 411 chemical pregnancies detected, 71.8% had P4-hCG ≥ 10.6 ng/ml (group A), while 28.2% had P4-hCG < 10.6 ng/ml. Of the cycles with P4-hCG < 10.6 ng/ml, 64.7% (group B) were supplemented with a higher dose of vaginal P4 (1,000 mg/day), while 35.3% (group C) were maintained on the same dose of vaginal micronized P4. The live birth rate was 71.9%, 96%, and 7.3% for groups A, B, and C, respectively. Conclusion: The likelihood to detect P4-hCG < 10.6 ng/ml decreased as the level of serum P4 the day before ET increased. The live birth rate (LBR) was shown to be significantly lower when P4 was low and not supplemented.

Comparison of IVF cycles reported in a voluntary ART registry with a mandatory registry in Spain.

BACKGROUND: Monitoring assisted reproductive technology (ART) is essential to evaluate the performance of fertility treatment and its impact on birth rates. In Europe, there are two kinds of ART registers: voluntary and mandatory. The validity of register data is very important with respect to the quality of register-based observational studies. The aim of this paper is to determine the degree of agreement between voluntary and mandatory ART registers. METHODS: The two sources for the data compared in this study (referring to 2005 and 2006) were FIVCAT.NET (an official compulsory Assisted Reproduction Registry within the Health Ministry of the Regional Government of Catalonia, to which all authorized clinics, both public and private, performing assisted reproduction in the region are obliged to report) and the register of the Spanish Fertility Society (SEF), to which data are provided on a voluntary basis. The SEF register data were divided into two groups: (i) data from clinics in Catalonia (SEF-CAT); (ii) data from the rest of Spain, excluding Catalonia (SEF-wCAT). The techniques compared were IVF cycle using patients' own eggs (IVF cycle) versus donor egg cycles. RESULTS: For IVF cycles, the voluntary ART register reflected 77.2% of those on the official one, but the corresponding figure was only 34.4% with respect to donated eggs. The variables analysed in the IVF cycle (insemination technique used, patients' age, number of embryos transferred, pregnancy rates, multiple pregnancies and deliveries) were similar in the three groups studied. However, we observed significant differences in donor egg cycles with regard to the insemination technique used, pregnancy rates and multiple pregnancies between the voluntary and the official register. CONCLUSIONS: Data from the voluntary ART register for IVF cycles are valid, but those for donor egg cycles are not. Further study is necessary to determine the reasons for this difference.

Impact of the Spanish Fertility Society guidelines on the number of embryos to transfer.

The multiple pregnancy rate in assisted reproduction treatment cycles depends, fundamentally, on the number of embryos transferred. It is essential that patients and professionals should have good practical guidelines on the best number of embryos to be transferred in each cycle in order to obtain high pregnancy rates with minimal risk of multiple pregnancies. This study analysed the impact made by the Spanish Fertility Society (SEF) guidelines on the number of embryos to be transferred, as regards the policies adopted at clinics in Spain and the resulting financial repercussions. Data were collected from the assisted reproduction treatment register of the SEF and compared over three periods of time: 2002-2003, with no legal regulation and no SEF guidelines; 2004, with only legal regulation; and 2005-2006, with legal regulation and SEF guidelines. The acceptance of SEF guidelines varies according to the IVF technique. The guidelines have led to a reduction in multiple pregnancy rates, especially concerning triplets, in patients' own-egg and with donor-egg cycles. Even without full implantation, these results validate the clinical utility of the SEF guidelines. They constitute a useful tool to reduce the incidence of the principal adverse effect of treatment cycles: multiple pregnancies. The multiple pregnancy rate in assisted reproduction cycles depends fundamentally on the number of embryos transferred. It is essential that patients and professionals should have good practical guidelines on the best number of embryos to be transferred in each cycle in order to obtain high pregnancy rates with minimal risk of multiple pregnancies. The purpose of this study was to analyse the impact made by the Spanish Fertility Society (SEF) guidelines on the number of embryos to be transferred, as regards the policies adopted at clinics in Spain, and the resulting financial repercussions. Data were collected from the assisted reproduction register of the SEF and compared over three periods of time: 2002-2003, when there was no legal regulation and no SEF guidelines; 2004, when there was only legal regulation; and 2005-2006, when there was legal regulation and SEF guidelines. The degree of acceptance of SEF guidelines varies according to the IVF technique employed. The guidelines have led to a reduction in multiple pregnancy rates, especially concerning triplets, using patients' own eggs and with donor eggs. The reduction in the financial cost of deliveries achieved in the years 2005-2006 ranged from 890,187 to 18,593,242 euros, and the incremental cost per percentage point of multiple pregnancy avoided is 2,989,613 euros. In conclusion, even without full implementation, these results validate the clinical utility of the SEF guidelines. They constitute a useful tool to reduce the incidence of the principal adverse effect of assisted reproduction cycles, namely multiple pregnancies.

Assisted reproductive technology and ovarian cancer.

Ovarian cancer has the highest mortality among all gynaecological cancers, being multiparity and oral contraceptive use the most important protective factors. According to both the "incessant ovulation" and "increased gonadotrophin" theories, fertility drugs might have an association with the development of ovarian cancer, as has been reported by some studies. However, infertility and nulliparity may act as confounding factors and most studies regarding this issue are hampered by methodological limitations. It seems that female infertility may be associated with a modest increase in ovarian cancer risk in those patients who remain nulligravid despite long periods of unprotected intercourse. Globally, most studies are reassuring in not showing a link between the use of fertility drugs and an increased risk of ovarian cancer. Nonetheless, further research in well-designed studies is warranted.

Couples' opinions regarding the fate of surplus frozen embryos.

With the passing of Act 45/2003, research with viable human embryos became legal in Spain. Since then, Institut Universitari Dexeus has been in contact with couples whose embryos had been frozen for more than 2 years to inform them about the new legal options and gather their opinions. A reply was received from 35.9% of the couples contacted, with the following results: 33.3% wished to preserve the embryos for their own use, 30.0% wished to donate the embryos for embryonic stem cell research, 20.2% wished to donate the embryos to third parties for reproductive purposes and 10.3% wished to terminate the cryopreservation process without further use. The couples who chose to donate the embryos for research were asked to give written informed consent to the donation of their embryos for a specific project. The possibility of donating embryos for research has been well received by the couples, and offers a solution to those who wish to make neither a further attempt for pregnancy nor a donation with reproductive goals. Donation for research purposes is considered a preferable alternative to disposal.

Assisted reproductive technologies in public and private clinics.

The aim of this study was to analyse the influence of the type of service provided by assisted reproduction clinics. The activities, treatment patterns and results achieved by assisted reproduction centres in Spain were examined, comparing public and private clinics. A retrospective study was carried out using the Assisted Reproductive Technology Register of the Spanish Fertility Society for 2002-2004. The results showed that 74%, 96% and 99% of IVF/intracytoplasmic sperm injection, oocyte donation and preimplantation genetic diagnosis cycles, respectively, were carried out in the private sector. Public clinics performed proportionally more transfers of three embryos than the private clinics (48.1% versus 41.7%). More elective transfers were performed in private clinics. Pregnancy rates per cycle started, per puncture and per transfer were significantly higher among private than public clinics (29.1%, 32.7% and 35.9% versus 25.2%, 28.5% and 32.6%, respectively) (P < 0.05). Implantation rate has risen year on year in both types of clinic and was significantly higher (P < 0.05), every year, among the private clinics. The multiple-pregnancy rate was significantly higher among the private clinics (30.8% versus 26.4%) (P < 0.05). In conclusion, differences exist between public and private clinics as regards to their volume of activity, the range of services offered, clinical practice and results achieved.

Human seminal plasma allergy and successful pregnancy.

Human seminal plasma allergy in women is an uncommon phenomenon. A great variety of reactions ranging from local swelling to generalized systemic reactions have been described, and local symptoms have often been misdiagnosed as chronic vulvovaginitis. Sperm barriers, such as condoms, are the most widely advocated method for avoiding these reactions; however this is not acceptable to couples who wish to have children. We present a case of a woman with human seminal plasma allergy who became pregnant after a fourth cycle of artificial insemination. Sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblotting showing an IgE binding band at 28kDa in the husband's seminal fluid identified the culprit allergen. Artificial insemination is an effective way to achieve a pregnancy in patients with seminal plasma allergy.

Stimulation protocols for poor responders and aged women.

There is a general consensus on the clinical fact that the more embryos replaced the higher pregnancy rates are achieved. For this reason those IVF cycles with a low response and a reduced number of oocytes and embryos will have very few chances of producing a pregnancy. It is very important to diagnose, by means of the anamnesis and hormonal tests which patients are most likely to present a poor response to conventional ovarian stimulation protocols. It is mandatory to know the patient's plasmatic levels of FSH and estradiol together with personal data such as the age and the previous history of the patient. Only young poor responders with a normal basal hormonal profile will have some chances that by applying new protocols and combining new drugs, improve their response and have higher pregnancy rates. For the old poor responders who have already failed to alternative protocols including natural cycles, oocyte donation is the last and best hope.

Spermatozoa selection in discontinuous Percoll gradients for use in artificial insemination.

In a preliminary study of the ejaculate of 93 men, changes in motility and hypo-osmotic swelling before and after sperm separation by discontinuous Percoll gradients were evaluated. Both parameters improved significantly (P less than 0.01) in Percoll-separated spermatozoa. In a second stage, 99 couples underwent intrauterine insemination of separated semen by Percoll gradients. The population had infertility for a mean of 5.6 years. In a 1-year period, a total of 344 intrauterine insemination cycles were completed. Failure was considered when conception did not occur within four treatment cycles. The mean number of cycles per successful couple before pregnancy was 1.52. An overall 21% pregnancy rate was achieved (16% for oligoasthenospermia and 24% for asthenospermia). Sperm separation in Percoll gradients is a useful technique for intrauterine insemination in some cases of male subfertility.

Prevention of multiple pregnancy following IVF in Spain.

Since the development of assisted reproduction techniques most countries have witnessed increased rates of multiple pregnancy. Despite the guidelines proposed by various scientific societies these rates continue to be abnormally high. In Spain, as in other Mediterranean countries, a greater number of embryos are transferred than in northern and central European countries and the incidence of multiple pregnancies is greater in comparison. Effective strategies must be established to prevent multiple pregnancy without reducing overall pregnancy rates. In the authors' institute, taking into account the authors' experience, the relevant literature, and despite the limitation of retrospective studies, it is recommended that a maximum of two embryos are transferred in young women with good quality embryos at the time of transfer. The transfer of three embryos is only recommended in women >or=38 years who have one or no good quality embryos available at the time of transfer. The responsibility for preventing multiple pregnancy lies with health professionals, who must be aware of the risks involved in twin and triplet pregnancy. Couples must be provided with objective information before starting an IVF cycle. Professional societies should highlight the problem and make suitable recommendations.

A prospective trial comparing oocyte donor ovarian response and recipient pregnancy rates between suppression with gonadotrophin-releasing hormone agonist (GnRHa) alone and dual suppression with a contraceptive vaginal ring and GnRH.

BACKGROUND: Contraceptive treatment before gonadotrophin-releasing hormone agonist administration presents advantages in women with a tendency to hyper-response and simplifies donor-recipient treatment synchronization. This study compares response to gonadotrophin stimulation under hypophyseal suppression in oocyte donors with or without vaginal contraceptive pretreatment. METHODS: One hundred and ninety oocyte donors were recruited in a single centre and prospectively assigned to one of two treatment groups, according to the day of the week menstruation initiated: Group VC-, no prior vaginal contraceptive and Group VC+, prior vaginal contraceptive. RESULTS: VC+ patients presented a significantly higher cancellation rate, lower plasma estradiol levels and fewer follicles >12 mm on the day of hCG, versus the VC- group. Number of oocytes recovered was significantly lower in the VC+ group. All the cases of severe ovarian hyperstimulation syndrome (SOHSS) were in the VC- group. Pregnancy rates by embryo transfer to synchronic recipients were similar between VC+ and VC- (59.5 versus 57.9%, respectively). CONCLUSIONS: Vaginal contraceptive pretreatment resulted in a higher ovarian suppression, whereas SOHSS rate was lower than in donors who did not receive pretreatment. There were no differences in pregnancy rates between the two groups of synchronic oocyte recipients.

Pregnancy after the replacement of a frozen-thawed embryo with less than 50% intact blastomeres.

Early embryo freezing with saccharose and propanediol gives a survival rate of 62% of the embryos if 4 cell embryos with only one intact blastomere after thawing are included. The first pregnancy achieved with such an embryo is reported as well as preliminary results obtained in our IVF programme using the French method.

[Results of conjugal artificial insemination using Percoll]. / Résultats de l'insémination artificielle conjugale (IAC) après Percoll.

Selection of spermatozoa on Percoll's medium has enabled to obtain 33 pregnancies in 217 couples. This simple and inexpensive technique, which is most successful during the first nine months, deserves to be attempted, in case of deficient sperm, before contemplating more complex techniques.

Risk factors for high-order multiple implantation after ovarian stimulation with gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a single centre.

BACKGROUND: High-order multiple pregnancies (triplets or more) have a large adverse impact on perinatal morbidity and mortality as well as important economic consequences. Most triplets and higher births are due to ovulation induction alone or in combination with intrauterine insemination (IUI) rather than to in-vitro fertilization (IVF). The present investigation was undertaken to determine whether there were specific variables that related to patient clinical characteristics (age of the woman, duration of infertility, type of infertility, body mass index, basal FSH and LH concentrations), treatment characteristics (initial dose of gonadotrophins, total dose of gonadotrophins administered, number of days of ovarian stimulation, insemination procedure, number of spermatozoa inseminated in patients undergoing IUI, type of luteal support), and ovarian response (oestradiol serum concentrations, number and size of follicles) that might be associated with the occurrence of high-order multiple implantation in order to develop a prediction model. METHODS: This study employed univariate, multivariate and receiver-operating characteristic (ROC) analysis of a large series of 1878 consecutive pregnancies obtained in cycles stimulated with gonadotrophins. Of them, 1771 (94.3%) were low-order pregnancies (1477 singletons and 294 pairs of twins) and 107 (5.7%) were high-order pregnancies. RESULTS: Predictive variables in the multivariate analysis were age of the woman, serum oestradiol concentrations and number of follicles >10 mm on the day of HCG injection. Stratification of the number of follicles into three categories (1 to 3, 4 to 5, and >5 follicles respectively), peak serum oestradiol and woman's age according to the ROC curves, showed that the risk of high-order multiple implantation correlated significantly with increasing total number of follicles and was significantly increased in women with a serum oestradiol >862 pg/ml and aged < or =32 years. CONCLUSIONS: This three-variable model can help to identify patients at high-risk for high-order multiple pregnancy in ovulation induction cycles.

Comparison of the role of cervical and intrauterine insemination techniques on the incidence of multiple pregnancy after artificial insemination with donor sperm.

PURPOSE: Our purpose was to investigate the role of the insemination technique used in an artificial insemination program with donor sperm (AID) in multiple pregnancy rates. METHODS: We carried out a retrospective nonrandom analysis of 300 pregnancies corresponding to 300 cycles in women from our Artificial Insemination Donor Sperm Program. All cycles were stimulated with gonadotropins. Single and multiple pregnancy cycles and intracervical and intrauterine pregnant cycles were compared. RESULTS: Intracervical insemination was performed in 173 cycles (58%), and intrauterine insemination in 127 (42%). Two hundred twenty-three pregnancies were single (74%), and 77 multiple (26%). In multiple pregnancy cycles, initial dose and mean total daily dose of gonadotropins, plasma estradiol levels, and number of follicles > or = 14 mm were significantly higher compared to those in single pregnancy cycles. Multiple pregnancy rte was significantly higher among pregnancies after intrauterine insemination (32%) than after intracervical insemination (21%). CONCLUSIONS: The intrauterine technique of insemination in AID-stimulated cycles with gonadotropins is related to multiple pregnancy risk.

Inadvertent gonadotrophin-releasing hormone agonist (GnRHa) administration in the luteal phase may improve fecundity in in-vitro fertilization patients.

Spontaneous pregnancies associated with inadvertent periconceptional administration of a gonadotrophin-releasing hormone agonist (GnRHa) occur in approximately 1% of in-vitro fertilization (IVF) cycles. The two main issues to be considered in these circumstances are the luteolytic effect of the agonist and embryotoxicity. In addition, some authors have suggested a higher incidence of ectopic implantations. In view of these concerns, we report on 15 patients who conceived during pituitary desensitization with a GnRHa in the luteal phase of the menstrual cycle, and review the literature on the subject. A detailed analysis of the data available so far, which include 59 pregnancies exposed to GnRHa, shows that: (i) there is no clinical evidence for impaired luteal function, and hormonal supplementation does not improve pregnancy outcome; (ii) with only two cases of reported minor malformations among 37 deliveries, both having a genetic component, there is no evidence of teratogenic effects; and (iii) ectopic implantations in these circumstances are related to tubal disease but not to the drug. Considering the long history of infertility in these patients who had previously been treated unsuccessfully by different therapeutic modalities, it is likely that the occurrence of those pregnancies is not merely coincidental and that GnRHa might have a positive role in fecundity. The improved fecundity may be explained by the mechanisms of luteinizing hormone action in the corpus luteum.

Indications for oocyte donation.

Donated oocytes were transferred on 92 occasions to 87 women without gonadal function and 5 with functional ovaries. Twenty-three pregnancies were established (25% pregnancy rate), 9 after transfer of fresh embryos in 30 synchronous donor and recipient cycles and 14 after transfers of frozen-thawed embryos in 62 asynchronous donor and recipient cycles. Twenty-two pregnancies were obtained in agonadal patients (25.3% pregnancy rate) and 1 in a gonadal woman (20% pregnancy rate). Pregnant women were younger than those who did not become pregnant, but the difference was not significant. The pregnancy rate was higher when intra-Fallopian transfer was performed (46%) as compared with intrauterine transfer (21.5%) and when micronized progesterone was given intravaginally (pregnancy rate 30.3%) as compared to intramuscularly injected natural progesterone in oil (pregnancy rate 22%). Twenty healthy infants have been born including one set of twins; four pregnancies miscarried.