Embryo reduction in multifetal pregnancies using saline injection: comparison between the transvaginal and the transabdominal approach.

A total of 30 patients with multifetal pregnancies, all resulting from treatment with superovulatory agents or assisted reproductive techniques, underwent embryo reduction. All patients had three or more fetuses (one sextuplet, two quintuplets, seven quadruplets and 20 triplets). The procedure was carried out using intra-embryonal injection of 0.9% sodium chloride solution. Embryo reduction was carried out via the transabdominal approach in 10 patients, performed at 11-12 weeks of gestation, and via the transvaginal route in 20 other patients, at 8-10 weeks of gestation. In the transabdominal group, one patient aborted following repeated attempts at embryo reduction while the other nine gave birth to healthy newborns (eight twins and one triplet). In the transvaginal group, four pregnancies are currently ongoing (all beyond 28 weeks of gestation), 14 pregnancies resulted in a delivery of at least one live newborn (13 twins and one singleton), one patient had a late abortion at 24 weeks' gestation and another was delivered at 27 weeks' gestation due to severe pre-eclampsia. Transvaginal ultrasound-guided needle procedures are commonly practised in most in-vitro fertilization units. The employment of this route for embryo reduction, performed at an earlier gestational age and with the use of a non-toxic substance such as 0.9% saline solution, is advocated.     

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.     

Predicting ongoing pregnancy following ovulation induction with recombinant FSH in women with polycystic ovary syndrome

BACKGROUND: Ovulation induction with recombinant FSH (rFSH) is common in women with polycystic ovary syndrome (PCOS) not responding to clomiphene citrate treatment, despite the associated risk of multiple pregnancies. We analysed clinical, ultrasonographic and endocrine parameters during initial screening of women with clomiphene citrate-resistant PCOS as predictors of ongoing pregnancy within 12 months of treatment following ovulation induction with rFSH. METHODS: Eighty-five women were allocated to receive rFSH as part of a multicentre clinical trial. rFSH was administered in a chronic low-dose step-up protocol. The primary end-point was an ongoing pregnancy within 12 months. A logistic model was built using clinical, ultrasonographic and endocrine parameters to predict the response to rFSH treatment, adjusted for the number of cycles performed. RESULTS: In total, 85 women underwent 272 treatment cycles with rFSH, of which 57 women (67%) achieved an ongoing pregnancy. Oligomenorrhoea, shorter duration of infertility and a lower free androgen index (FAI) were associated with higher chances of an ongoing pregnancy, resulting in a predictive model with a modest discriminative power (area under the curve 0.72, 95% confidence interval 0.64-0.79) that allowed us to distinguish between women with a probability of <5% of attaining an ongoing pregnancy and women with a probability of >25% of doing so. CONCLUSION: A model consisting of oligo/amenorrhoea, duration of infertility and FAI level allowed a distinction to be made between women with a poor chance and women with a good chance of achieving an ongoing pregnancy.     

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.     

Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.     

Hydatidiform mole coexisting with a fetus in twin gestation following gonadotrophin induction of ovulation.

A case is presented of a twin gestation comprising a grossly normal fetus and placenta coexisting with a separate hydatidiform mole which ended in an abortion. Both developed following ovulation induction with human menopausal gonadotrophin and human chorionic gonadotrophin. The literature is reviewed and clinical aspects of this rare entity are discussed.     

Modern use of clomiphene citrate in induction of ovulation

Clomiphene citrate is the treatment of first choice in the managementof infertility in normally oestrogenized, anovulatory women(WH0 group II). The majority of women with 'pure' anovulatoryinfertility respond to treatment with clomiphene citrate. Therates of pregnancy and miscarriage are close to those expectedin a normal fertile population. Basal hormone concentrationsdo not predict outcome. An increased body mass index is theonly factor which is consistently associated with a decreasedresponse to clomiphene citrate; it follows therefore, that weightreduction should be an important part of therapy in anovulatorywomen. According to our data, only an increased luteinizinghormone value immediately post clomiphene citrate predictedan adverse pregnancy outcome in women who conceived. Clomiphenecitrate, along with other ovulation induction therapies, cancause multiple follicular development, with a risk of ovarianhyperstimulation and multiple pregnancy. Ultrasound monitoringof treatment is important in order to choose the appropriatedose of clomiphene citrate in subsequent cycles and to minimizethe risks of hyperstimulation and multiple pregnancy. When coupleswith other factors contributing to subfertility are excluded,the cumulative conception rate continues to rise after 6 monthsof treatment with clomiphene citrate, reaches a plateau by treatmentcycle 12 and approaches that of the normal population. It hasbeen reported that prolonged use of clomiphene citrate may beassociated with an increased risk of a borderline or invasiveovarian tumour. Taking into consideration these observations,we recommend that anovulatory women responsive to clomiphenecitrate should be treated for at least 6 cycles before consideringmore complex or invasive methods of ovulation induction, andthat treatment should probably be limited to a maximum of 12cycles.     

Effect of cyclofenil on hormonal dynamics, follicular development and cervical mucus in normal and oligomenorrhoeic women.

Cyclofenil is a triphenylethylene derivative, similar in structure to clomiphene citrate, which is used to induce ovulation in anovulatory women. The effects of cyclofenil on a group of 10 normal cyclic and 10 oligomenorrhoeic subjects were examined in a double blind controlled cross-over study. Both groups of women were administered either cyclofenil or, following a washout cycle, a placebo in two treatment cycles. Urinary oestrone and pregnanediol excretion were measured daily and ultrasound scans performed to assess follicular development. Frequent sampling of blood was performed on day 6 to study luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile release. Cervical mucus changes and sperm-cervical mucus interaction were studied after identification of the LH peak. There were no significant differences between cyclofenil and placebo cycles in the following: ovulation rates, daily urinary oestrone and pregnanediol excretion, the number or size of developing follicles, LH pulsatility (parameters studied: number of peaks, pulse interval, pulse amplitude, pulse area and mean nadir LH), mean FSH level on day 6, cervical mucus and sperm-cervical mucus interaction. In view of our inability to demonstrate an effect on any parameter of endocrine function in normal and oligomenorrhoeic women, these results throw doubt on the therapeutic value of cyclofenil in its present dosage and formulation.     

Maternal and neonatal outcomes in dichorionic twin pregnancies following IVF treatment: a hospital-based comparative study

Aim: To compare maternal, and neonatal outcomes in IVF/ICSI and spontaneously conceived dichorionic twin pregnancy. Method: We collected data regarding dichorionic twin pregnancies following in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI, n=162) with the transfer of fresh embryos as well as data regarding spontaneously conceived pregnancies (n=213) delivered after 28 weeks of gestation at the Department of Obstetrics and Gynecology, Renmin Hospital in Wuhan in the years of 2010-2013. We then compared maternal and neonatal outcomes between IVF/ICSI and spontaneous dichorionic twin pregnancies, with a subgroup analysis separating traditional IVF from ICSI pregnancies. Odds ratios (OR) for associations between IVF/ICSI and pregnancy outcomes were adjusted for maternal factors. Results: The mean maternal age and the percentage of primiparous women were significantly higher in the IVF/ICSI group. Multivariate analysis revealed that maternal outcomes were comparable in both groups with/without adjustment for maternal age and parity. However, IVF/ICSI twins were less likely to have birth weight discordance than those spontaneously conceived (unadjusted OR=0.526, 95% CI 0.297-0.932; adjusted OR=0.486, 95% CI 0.255-0.856). In subgroup analyses, these associations were confirmed in the IVF (adjusted OR=0.496, 95% CI 0.265-0.926), but not in the ICSI group (adjusted OR=0.500, 95% CI 0.139-1.807). Conclusion: IVF/ICSI treatment was not a risk factor for adverse maternal neonatal outcomes, but the risk for birth weight discordance is lower among IVF/ICSI twins.     

Late paternity and stillbirth risk

BACKGROUND: The role of paternal ageing on the incidence of some genetic diseases in offspring depends on the hypothesis that spontaneous mutations accumulate due to continuous cell divisions during spermatogenesis. We examined the effect of paternal age on the complex multifactorial character, stillbirth. METHODS: In 3,619,647 Italian singletons born in 1990-1996 we evaluated stillbirth risk as a function of paternal ageing by means of multiple logistic regression models, which included maternal age and family education, as categorical covariates and interactions. The categorical risk was estimated for mothers and fathers beyond threshold ages of 35 and 40 years, respectively. RESULTS: Stillbirth risk increases with paternal ageing in mothers > or =30 years old, and maternal age and family education modify the impact. In families with low education, the risk accounts for odds ratio (OR) 1.015 [95% confidence interval (CI) 1.01-1.02] in mothers aged 30-34 years, and for OR 1.032 (95% CI 1.02-1.04) in mothers aged > or =35 years; in families with higher education the risk accounts for OR 1.008 (95% CI 1.00-1.02) and OR 1.025 (95% CI 1.01-1.04), respectively, in mothers aged 30-34 and > or =35 years. In these latter families, for mothers aged <35 and fathers > or =40 years the risk accounts for OR 1.12 (95% CI 1.00-1.25). CONCLUSIONS: The effect of paternal ageing on stillbirth risk is revealed in mothers aged > or =30 years and is modified by family education. In mothers aged 30-34 years from families with high education, the increase imputable to paternal ageing might be indicative of a genetic component.     

Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome

BACKGROUND: Laparoscopic ovarian diathermy (LOD) is currently accepted asa successful second-line treatment for ovulation induction (OI)in clomiphene citrate (CC)-resistant women with polycystic ovarysyndrome (PCOS). The aim of this study was to test the hypothesisthat LOD may be superior to CC as a first-line treatment. METHODS: The study included 72 anovulatory women with PCOS who were randomizedto LOD (n = 36) or CC (n = 36). Women who remained anovulatoryafter LOD were offered CC. Similarly, women receiving CC whofailed to ovulate or conceive were offered LOD. Pregnancy rateswere compared between the two groups using ² and odds ratiowith 95% confidence interval (OR, 95% CI). RESULTS: After randomization, six women conceived before starting treatmentand another patient postponed treatment. The remaining 65 womenreceived the treatment (33 underwent LOD and 32 received CC).After the primary treatment, more pregnancies (44%) occurredin women receiving CC than in those undergoing LOD (27%), althoughthe difference did not reach statistical significance [P = 0.13,OR 2.1 (0.7 – 5.8)]. After adding the second treatment,the pregnancy rate was still higher, but to a less extent, inthe CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 – 4.2)]. CONCLUSIONS: LOD is not superior to CC as a first-line method of OI in womenwith PCOS. The trial is registered with ClinicalTrials.gov withan identifier number NCT00220545 [ClinicalTrials.gov] .     

Laparoscopic removal of an abdominal pregnancy adherent to the appendix after ovulation induction with human menopausal gonadotrophin

The laparoscopic management of tubal pregnancies has becomea standard form of treatment. We present, for the first time,a successful laparoscopic approach in the management of earlyabdominal pregnancy. Although it is difficult to reach conclusionsfrom such limited published experience, it nevertheless appearsthat early abdominal pregnancies can be treated via operativelaparoscopy. The possible advantages of such a therapeutic approachinclude lower morbidity and mortality, and a better fertilityprognosis.     

Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis

BACKGROUND: Both selective estrogen receptor modulators, tamoxifen and clomiphene have been used for ovulation induction for patients with anovulatory infertility. This meta-analysis sought to compare the effectiveness of tamoxifen to clomiphene for the induction of ovulation and achievement of pregnancy. METHODS: We searched MEDLINE, BIOSIS, PreMEDLINE, CINAHL, International Pharmaceutical Abstracts, DDSR, ACP Journal Club, DARE and CCTR, along with reference lists and national experts. Inclusion criteria were prospective clinical trials, which compared tamoxifen and clomiphene for ovulation induction in infertile couples with isolated anovulatory infertility. Main outcome measures were ovulation rate and clinical pregnancy rate. Pooled odds ratios were obtained using random effects meta-analysis. RESULTS: Four trials were included. After pooling all the trials, the use of tamoxifen or clomiphene citrate resulted in similar ovulation rates [odds ratio (OR) 0.755, 95% confidence interval (CI) 0.513-1.111]. There was no benefit of tamoxifen over clomiphene citrate in achievement of pregnancy per cycle (OR 1.056, 95% CI 0.583-1.912) or per ovulatory cycle (OR 1.162, 95% CI 0.632-2.134). CONCLUSIONS: Clomiphene citrate and tamoxifen are equally effective in inducing ovulation. Although data regarding pregnancy rates and outcome are limited, there does not appear to be a significant benefit of one medication over the other.     

High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies

Antiphospholipid antibodies (APA), lupus anticoagulant (LA)and/or anticardiolipin antibodies (ACA), are associated withthrombosis and recurrent miscarriage. We studied the outcomeof 20 pregnancies in women (median age 32 years; range 23–41)with APA (14 LA positive; three immunoglobulin (Ig) G ACA positive;two IgM ACA positive and one LA and IgG ACA positive) and historyof recurrent miscarriage (median 4; range 3–11) who declinedpharmacological treatment in their next pregnancy. Comparisonwas made with a cohort of 100 consecutive women (median age33 years; range 23–44) with recurrent miscarriage (median4; range 3–10), in whom no underlying cause to accountfor their pregnancy losses was found. Of the 20 women with APA,18 (90%) miscarried compared to 34 of the 100 women (34%) withnormal investigations (P < 0.001). The majority (94%) ofmiscarriages in women with APA occurred in the first trimester.Fetal heart activity was seen prior to fetal death in 86% ofwomen with APA compared to 43% of women with normal investigations(P < 0.01). The first trimester loss of embryonic pregnanciesis the most common type of miscarriage in women with APA. Thismay be a result of defective implantation and subsequent placentation.     

Obstetric outcome of 424 pregnancies after intracytoplasmic sperm injection

An evaluation of the outcome of pregnancies resulting from intracytoplasmicsperm injection for severe male factor infertility was conductedby analysing the data obtained from the patients and/or theirobstetrician/gynaecologist on standardized questionnaires. Thedata from 424 pregnancies between April 1991 and September 1994were analysed. Early pregnancy loss before 16 weeks occurredin 99 cases (23.3%), including 48 clinical abortions (11.3%),47subclinical pregnancies (11.1%) and four ectopic pregnancies(0.9%). Vanishing twins and triplets, which could be regardedas early embryonic wastage, were found in 36 cases (8.5%). Onepregnancy was interrupted at week 15 of gestation because ofanhydramnios, and four pregnancies (0.9%) ended in spontaneouslate abortions before 26 weeks. A total of 320 pregnancies (75.5%)resulted in the birth of at least one child; 222 of these (69.3%)were singletons, 93 were twins (29.1%) and five were triplets(1.6%). The problems of prematurity and low birthweight wereespecially related to the multiplicity of pregnancies. Furthermore,from among the total of 423 babies born, we have observed threecases of stillbirth and five cases of neonatal mortality. Theperinatal mortality rate was therefore 18.9 per 1000 births.The results of this study show that the obstetric outcome ofthese pregnancies was similar to that obtained after conventionalin-vitro fertilization and other assisted reproduction techniques.     

The role of early post-implantation beta-HCG levels in the outcome of pregnancies following in-vitro fertilization

Daily plasma beta-HCG levels from days 11 to 18 after ovum retrieval(OR) were evaluated in a group of 73 women who became pregnantfollowing in-vitro fertilization and embryo replacement (IVF-ER).The 47 patients who had a normal ongoing pregnancy could bedistinguished from the 26 patients with a pathological pregnancy(pre-clinical abortion, clinical abortion and tubal pregnancy)by the mean daily beta-HCG levels, their mean daily increaseand the intercept and slope of the beta-HCG regression analysis.The mean daily beta-HCG levels of the normal pregnancies weresignificantly higher than: (i) pre-clinical abortions on days12–18 after OR; (ii) clinical abortions on days 12–16;and (iii) tubal pregnancies on days 12–17. Using quadraticdiscriminant analysis, normal and pathological pregnancies couldalso be distinguished by their absolute beta-HCG levels on day13 after OR with 27.6 mIU/ml being the cut-off point. Our resultsindicate that the outcome of pregnancy following IVF-ER couldbe predicted with a high degree of probability by monitoringdaily beta-HCG levels within the first 2 weeks following OR.     

Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea

Pulsatile administration of gonadotrophin releasing hormone(GnRH) is a very effective treatment for induction of ovulationin hypothalamic amenorrhoea (HA). Thirty-seven women have beentreated for a total of 117 cycles which resulted in 42 pregnancies–fourtreatment failures occurred. If these cycles are excluded, the42 pregnancies were obtained within 2.3 cycles. One twin pregancyoccurred and no hyperstimulation was observed. The treatmentwas administered intravenously with a dosage schedule basedon the grading of HA. We concluded that pulsatile GnRH was safeand very successful in induction of pregnancy in HA. Other indications(polycystic ovary syndrome and luteal phase defect) remain muchless suitable for this treatment.     

Obstetrical results after embryonic reductions performed on 34 multiple pregnancies

Thirty-four women with multiple pregnancies (three or more fetuses) underwent embryonic reduction in order to reduce abortions, premature births or fetal growth-retardation by obtention of twins. Four early abortions occurred. Thirty pregnancies reached term and out of 60 fetuses, 58 infants were born alive. Fetal death in utero of one twin occurred in two pregnancies. The mean term until delivery was 36 +/- 2.8 weeks gestation and the prematurity rate was 51.7%. Of 55 neonates, 25 were underweight within the 10th percentile and 10 out of 55 neonates were underweight below the 3rd percentile. There were three deaths in the early neonatal period. The rate of perinatal mortality was 8.3%. Fifty-four children are currently healthy and one child has a mild axial hypotonia. A reduction in prematurity was observed with a gain of 2 weeks on reported data concerning triplet pregnancies. The rate of low-birth-weight infants was high, 63.5% being underweight at birth.     

Reproductive features in women developing ovarian granulosa cell tumour at a fertile age

Ovarian granulosa cell tumour (GCT) is a rare malignancy, which has been linked to both infertility and infertility treatment with ovulation inducers. The reproductive features were analysed of 146 women with GCT diagnosed between 1956 and 1996. During the study period no changes were found in the mean age (53 years), menopausal status (59% postmenopausal), parity (32% nulliparous) or tumour size or stage at diagnosis. The clinical features in women with GCT at fertile age were compared with GCT diagnosed later in life and to population-based data. Nulliparity (50%) and history of infertility (22%) were more frequent if the tumour occurred at fertile age (n = 50). Of the 12 infertile cases, seven had anovulatory infertility (58%); 11 occurred during the era of ovulation inducers, but only five had used these drugs (clomiphene citrate in five patients, gonadotrophins in two, and tamoxifen in one patient) and no patient had undergone in-vitro fertilization. Endometrial hyperplasia was associated with GCT at all ages, while endometrial cancer was found solely after the age of 45 years. In conclusion, GCT at fertile age is associated with nulliparity and with a clinical presentation of anovulatory infertility, while GCT later in life is associated with a more normal average fertility pattern and with occurrence of endometrial cancer.     

Endocrinology: A 'sweet' indication for ovulation induction

In diabetic patients, euglycaemia at the thne of conceptionis crucial for the success of the pregnancy. In considerationof the difficulty in achieving and maintaining tight glycaemiccontrol for long periods, we administered clomiphene citrate,which is usually indicated in cases of absent or infrequentovulation, to enhance fecundability in 10 pregestational diabeticpatients. All conceived within one to three cydes of the drug,and nine delivered healthy term babies after uneventful pregnancies;one aborted spontaneously in the eighth gestatlonal week. Noeffect of the drug on the diabetes was noted as based on measurementsof glycosylated haemoglobin and fructosainine con centrationsand the absence of changes in the patients' insulin requirements.In the light of these successful results, and in view the importanceof euglycaemia at the beginning of diabetic pregnancies, wesuggest a new ‘sweet’ indication for the use ofclomiphene citrate.