Occurrence Of Multiple Pregnancies Research Articles

Prólogo al Simposio sobre Embarazo Múltiple

El Hospital Nacional Daniel Alcides Carrión del Callao, Perú, organizó recientemente bajo la conducción del Dr. Rommel Lacunza un simposio sobre Embarazo Múltiple, un tema poco revisado, pero cuya ocurrencia ha existido a través de los tiempos, algo más en las 3 a 4 últimas décadas(1). Hace algunos años, Hellin postuló que el embarazo gemelar ocurría en la proporción de 1 en 89 nacimientos, y que los embarazos triples, cuádruples y de mayor orden aparecían en la relación 1 en 892, 1:893, 1:89n(2). En Inglaterra y Gales, la incidencia de embarazos múltiples aumentó de 10 por 1 000 en 1980 a 16 por 1 000 en 2009, señalándose como causa importante el éxito de las técnicas de reproducción asistida y la ocurrencia de embarazos múltiples hasta en 24% de los casos en que se empleó la fertilización in vitro(1). En un estudio peruano, la incidencia de embarazo múltiple fue 1,1% en 314 078 recién nacidos, aumentando a 2,7% cuando se asoció a la preeclampsia(3). En la Red Latinoamericana de Reproducción Asistida, en su reporte de 2012, la frecuencia de parto múltiple fue 30,2% (27,8% dobles y 2,4% triples y mayores) en 47 326 procedimientos(4).

Single embryo transfer

Multiple pregnancies present significant problems for mothers and babies. The incidence of twin pregnancies has increased dramatically in the last 30 years, linked to the development of assisted reproductive technologies including in vitro fertilisation (IVF). The occurrence of multiple pregnancies after IVF is directly related to the number of embryos replaced during treatment. Policies to reduce the number of multiple pregnancies through limiting the numbers of embryos transferred have been successfully introduced in some parts of Europe. Anxieties that pregnancy rates would decline significantly after introduction of a policy of single embryo transfer have not been realised, particularly when the pregnancies derived from the transfer of additional cryopreserved embryos are taken into consideration. Obstacles to the introduction of such a policy in the UK relate to the commissioning arrangements for IVF and the competitive commercial environment in which IVF is provided. Continued high multiple pregnancy rates are not acceptable. IVF children should be given the best chance possible of safe delivery, at term, as singletons.

Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial

After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor.

20 years in vitro fertilization: what follows?

During the last two decades in-vitro fertilization (IVF) developed on a worldwide scale by increasing numbers of treated couples and by extending the medical indications. Existing treatment protocols have been optimized to such an extent that pregnancy rates over 30% are reached in many treatment units. Further improvements of the pregnancy rate may be achieved with assisted hatching, which is now the subject of a large European multicentric prospective study based on the University of Lausanne. On the other hand, the occurrence of multiple pregnancies, which is the main complication of IVF, may be limited by reducing the number of embryos replaced. Further improvements of treatment efficacy may result from the introduction of new medications, such as recombinant FSH or GnRH-antagonists, allowing for the adaptation of the treatment protocol used to the individual needs of each patient. A treatment protocol combining a GnRH-antagonist and gonadotropins may be particularly valuable in young patients for the purpose of avoiding the ovarian hyperstimulation syndrome. The major disadvantage of these novel medications consists of their increased costs. Therefore, a new treatment strategy is currently developed aiming at shortening the ovarian stimulation in combination of a prolongation of the laboratory phase. The in-vitro maturation of immature oocytes aspirated from small follicles previously primed with recombinant FSH has been shown to be a feasible alternative to the present treatment modalities. Cryopreservation of unfertilized oocytes together with in-vitro maturation may prove to be helpful for women prior to chemotherapy or radiation because of malignant diseases or for patients suffering from incipient ovarian failure. At present, there seems to be no alternative to assisted reproduction although the dominance of this technique may impede the development of more cause-related treatment strategies in infertility.

Supraphysiological serum relaxin concentration during pregnancy achieved by in-vitro fertilization is strongly correlated to the number of growing follicles in the treatment cycle.

In order to analyse the relationship between the ovarian response to stimulation in in-vitro fertilization (IVF) treatment cycles and relaxin concentrations during subsequent pregnancies, 31 healthy women pregnant after IVF treatment were studied prospectively. The maximum number of follicles observed from day -4 to day -2 in relation to ovum retrieval and the number of oocytes recovered were recorded. In addition, blood samples were drawn in the follicular phase, the luteal phase, early pregnancy and at gestational weeks 12, 16, 20, 27 and 35 to assess oestradiol, progesterone, human chorionic gonadotrophin and relaxin. The maximum numbers (mean +/- SEM) of follicles observed and oocytes recovered were 9.0 +/- 0.6 and 6.1 +/- 0.5 respectively. The supraphysiological mean relaxin values were strongly correlated to the maximum number of follicles observed (r = 0.72, P < 0.0001) and the number of oocytes recovered (r = 0.64, P < 0.0001), indicating that the source of increased relaxin production during IVF pregnancy might be the ovary. These results are supported by experimental data. In the present study, the occurrence of multiple pregnancy was not associated with higher relaxin concentrations, which is further support for the hypothesis that the ovary is the main source of serum relaxin.

Clomiphen-resistentes PCO-Syndrom: Die IVF-Behandlung als Alternative bei Versagen der Gonadotropinbehandlung

34 infertile patients with severe clomiphene-resistant polycystic ovary syndrome were treated with IVF/ET. Stimulation attempts with gonadotropins had resulted in multifollicular ovarian reactions, which did not allow standard ovulation induction using hCG due to the risk of multiple pregnancy. The resulting oocyte retrieval rates (87.4%/treatment cycle), embryo transfer rates (73.3%/oocyte retrieval) and pregnancy rates (24.2%/embryo transfer) approximately corresponded to the rates which are achieved in women with tubal failure using IVF/ET. Since strictly a maximum of 2 embryos was transferred, the occurrence of multiple pregnancies of higher degree could be avoided as opposed to standard gonadotropin therapy. The treatment so far only resulted in singleton pregnancies. The relatively high ovarian hyperstimulation rate (34.4%, primarily WHO stage I-II) could not be unequivocally lowered even by aspiration of all larger follicles.

The inability of preovulatory ovarian scan to predict multifetal pregnancy occurrence in a follow-up of induction of ovulation with menotropins

To establish the predictive role of preovulatory ovarian ultrasonography in the occurrence of multiple pregnancy after hMG and hCG treatment for anovulatory infertility. Prospective. Outpatient Infertility Clinic. Ninety-five anovulatory women who conceived after gonadotropin therapy. Induction of ovulation by hMG and hCG monitored by plasma E2 measurements and ovarian ultrasonography. All follicles visualized on the day of hCG administration were recorded and divided into the following four groups: group I, 10 to 12 mm; group II, 13 to 15 mm; group III, 16 to 18 mm; and group IV, 19 mm and larger. The sonographic findings were statistically evaluated to 80 singletons and 45 multiple pregnancies. No statistical correlation was found to exist between the number of follicles from the different groups and the number of fetuses. The number and sizes of follicles visualized on the day of hCG administration have no predictive value regarding the occurrence of a multiple pregnancy.

The relationship between embryo quality and the occurrence of multiple pregnancies

To study the relationship between the quality of the transferred embryos and the occurrence of multiple pregnancies. Embryo quality was defined by the cleavage rate and by morphological parameters such as blastomere size and the presence or absence of anucleate fragments.A retrospective analysis of 1,915 consecutive transfers of fresh embryos between January 1986 and December 1989.All the embryo transfers (ETs) were performed in patients from the in vitro fertilization program of the Center for Reproductive Medicine, Vrije Universiteit Brussel, Brussels, Belgium.We confirmed the relationship between the number of embryos transferred and the pregnancy rate (PR): 11.9% of the single, 19.0% of the double, and 34.1% of the triple ETs were successful. Thirty-one percent of these triple embryo replacements resulted in a multiple gestation. At the time of transfer (44 to 48 hours after insemination), we observed that embryos that had undergone at least two mitotic divisions implanted better than two-cell embryos of comparable morphological appearance (implantation rate per transferred embryo: 21.3% versus 12.3%, P less than 0.001) and that heavily fragmented embryos did not implant as well as embryos without or with fewer anucleate fragments (1.5% versus 14.1%, P less than 0.001). The PR, implantation rate, and the incidence of multiple pregnancies increased significantly with the number of good quality embryos that were transferred.Our study indicated that embryo quality based on morphological observations could predict the occurrence of multiple pregnancies.

The relationship between embryo quality and the occurrence of multiple pregnancies

To study the relationship between the quality of the transferred embryos and the occurrence of multiple pregnancies. Embryo quality was defined by the cleavage rate and by morphological parameters such as blastomere size and the presence or absence of anucleate fragments. A retrospective analysis of 1,915 consecutive transfers of fresh embryos between January 1986 and December 1989. All the embryo transfers (ETs) were performed in patients from the in vitro fertilization program of the Center for Reproductive Medicine, Vrije Universiteit Brussel, Brussels, Belgium. We confirmed the relationship between the number of embryos transferred and the pregnancy rate (PR): 11.9% of the single, 19.0% of the double, and 34.1% of the triple ETs were successful. Thirty-one percent of these triple embryo replacements resulted in a multiple gestation. At the time of transfer (44 to 48 hours after insemination), we observed that embryos that had undergone at least two mitotic divisions implanted better than two-cell embryos of comparable morphological appearance (implantation rate per transferred embryo: 21.3% versus 12.3%, P < 0.001) and that heavily fragmented embryos did not implant as well as embryos without or with fewer anucleate fragments (1.5% versus 14.1%, P < 0.001). The PR, implantation rate, and the incidence of multiple pregnancies increased significantly with the number of good quality embryos that were transferred. Our study indicated that embryo quality based on morphological observations could predict the occurrence of multiple pregnancies.

Can Ultrasonography Reliably Predict the Occurrence of Multiple Pregnancies in Gonadotropin Ovulation Induction?

A retrospective study of 78 patients with 106 stimulated conception cycles after successful gonadotrophin ovulation induction was made to analyze the relationship between the sizes and numbers of ovarian follicles seen on ultrasound and the eventual number of conceptions that resulted in each cycle. Fifteen cycles (14.2%) resulted in spontaneous abortions. There were 58 singleton pregnancies (54.8%), 26 sets of twins (24.5%), 6 sets of triplets (5.6%) and 1 set of quadruplets (0.9%). In 86 cycles with the last scans performed shortly before the ovulating dose of HCG, 3 or more mature follicles were found in 50 (58%). These cycles resulted in 31 (62%) singletons, 16 (32%) twin pregnancies and 3 (6%) triplet pregnancies. Pregnancies resulted even when there were no 'mature' follicles seen on scan. No statistical correlation was found between plurality of pregnancy and size or number of follicles, or oestradiol excretion on the day the ovulating dose of HCG was given, although high-order multiple pregnancies were more likely if the oestrogen excretion was more than 200 ug/24 hours (p = 0.001). The dosage of HCG correlated inversely with the occurrence of multiple pregnancies (p = 0.02). In conclusion, neither oestrogens nor ultrasonography could accurately predict multiple conceptions in gonadotrophin stimulated cycles.

Embryo scoring as a prognostic tool in IVF treatment.

A semi-quantitative and non-invasive method for scoring embryos obtained after in-vitro fertilization (IVF) has been defined, aiming at selection of embryos before transfer and at prognostic evaluation of IVF trials. Grading of embryos observed on the inverted microscope was essentially based on the amount of anucleate fragments expelled during early cleavage and on developmental speed. Embryos endowed with a high score were more often associated with pregnancy and in particular with the occurrence of multiple pregnancy. No difference was observed between scores attributed to embryos related to ongoing, aborted or chemical pregnancies. Average embryonic scores corresponding to double and triple transfers differed significantly in failures as well as pregnancies. The better quality of embryos replaced in triple transfers was also apparent from the significantly higher implantation rate per embryo observed in this group. From our results, five criteria including clinical data and embryonic scores can be derived for defining a high risk of multiple pregnancy prior to transfer. It might be warranted to replace only two embryos when these conditions are fulfilled.